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Presents a list of forthcoming papers on immunology, as of January 2003. Signaling transduction pathway for eotaxin- and interleukin-5 induced eosinophil shape change; Recognition of bovine respiratory syncytial virus proteins by bovine lymphocytes; Prevention of oral tolerance induction by administration of exogenous interleukins.

A list of forthcoming papers related to immunology is presented. These include "Variable influences of iodine on the T-cell recognition of a single thyroglobulin epitope," by Hong Jiang, "Triacylated lipoproteins derived from Mycoplasma pneumoniae activate NF-jB through TLR1 and TLR2," by Takashi Shimizu, and "Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and Th1/Th2 balance," by Alexander Borowsky and Kevin Kent Lloyd.

The article presents a list of forthcoming papers in the publication. These include "Dissection of spontaneous cytotoxicity by human intestinal intraepithelial lymphocytes: MIC on colon cancer triggers NKG2D-mediated lysis through fas ligand," "Myb proteins regulate expression of histone variant H2A.Z during thymocyte development," and "Importance of N-linked gycosylation in the functional expression of murine CD1d1."

A list of forthcoming papers related to immunology which are to be published is presented. They include "Prostaglandin E2 modulates dendric cell function during chlamydial genital infection," by Wei Liu and Kathleen Ann Kelly and "Dissection of spontaneous cytotoxicity by human intestinal intraepithelial lymphocytes: MIC on colon cancer triggers NKG2D-mediated lysis through Fas ligand," by Ellen Ebert and Veronika Groh.

The article lists the forthcoming papers on immunology which includes "Prostaglandin E2 modulates dendritic cell function during chlamydial genital infection," by Wei Liu and Kathleen Ann Kelly, "Role of endogenous 4-1BB in the development of systemic lupus erythematosus," by Dass Vinjay, Jae Choi and "Dissection of spontaneous cytotoxicity by human intestinal intraepithelial lymphocytes: MIC on colon cancer triggers NKG2D-mediated lysis through Fas ligand," by Ellen Ebert, Veronika Groh.

The article presents information on several manuscripts that will be published in the forthcoming issues of the journal "Immunology." Some of the manuscripts enlisted are: "Resistance to Re-Challenge in the Brown Norway Rat Model of Vasculitis is Not Always Complete and May Reveal Separate Effector and Regulatory Populations," by C. S. Vinen, D. R. Turner, D. B. G. Oliveira and D. Oliveira; "Identification and Characterization of Macaque CD89," by K. A. Rogers, F. Scinicariello, R. Attanasio and Roberta Attanasio; "Th Memory Clones With Identical TCR Rearrangement (nontransgenic), But Distinct Lymphokine Phenotype, Reveals Diverse and Novel Gene Expression," by C. M. Graham, D. B. Thomas and D. Thomas.

The article presents a list of articles related to immunology. The articles include "Monocyte-Derived Dendritic Cells From Horses Differ From DC of Humans and Mice," by Susanne Mauel, Falko Steinbach and Hanns Ludwig, "Extended Sequence Preferences for Oligodeoxyribonucleotide Activity," by Peter Lenert, Adam Goeken and Robert Ashman, "On the Logic of Positive Selection," by Melvin Cohn, "CTLA-4 Interacts With Stat5 and Inhibits Stat5-Mediated Transcription," by M. Srahna, L. Van Grunsven, J. Remacle and Peter Vandenberghe, and "Peritoneal Macrophages Supress T Cell Activation by Amino Acid Catabolism," by R. Matlack, K. Yeh, L. Rosini, D. Gonzalez, J. Taylor, D. Silberman, A. Pennello and James Riggs.

New short-lived strains of mice (SAM-P), which have been developed by Takeda et al. (1981), show a defective antibody response to T dependent (TD) antigen in vitro, as demonstrated in the accompanying paper (see page 419). In the present study, we investigated the cellular site of the defect, using a cell culture system. In this paper, it is demonstrated that T-helper (Th) cell activity for the antibody response to TD antigen is impaired, while other cellular immune responses, e.g. mixed leucocyte reaction, cytotoxic T-lymphocyte response, and delayed-type hypersensitivity reaction, are normal. These results suggest that the defect in T-helper subset is limited in helper function for the antibody response, and that the helper function for the cell-mediated immune responses is intact. These two functions of the T-helper subset are apparently regulated in a different manner. The SAM-P strains of mice may thus serve as an appropriate model for studying functional heterogeneity in T-helper/inducer cell subsets. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is aetiologically linked to immunological ageing and dysfunction. One aspect of this is the altered neutrophil-to-lymphocyte ratio (NLR), which in other domains have been associated with inflammation and angiogenesis, and therefore investigated in patients with AMD in several papers. In this systematic review and meta-analysis, we summarize findings in patients with AMD in relation to NLR, both qualitatively and quantitatively. We searched PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central and identified six studies from where we extracted data on 1178 individuals (777 patients with AMD and 401 healthy controls). Patients with AMD had a higher NLR (weighted mean difference: 0.37, CI 95% 0.08 to 0.66, p = 0.013) when compared to healthy controls. In subgroup analyses, we did not find a significant difference between patients with dry AMD and healthy controls (weighted mean difference: 0.34, CI 95% -0.03 to 0.69, p = 0.068), but did find a strong significant difference between patients with neovascular AMD and healthy controls (weighted mean difference: 0.54, CI 95% 0.23 to 0.86, p = 0.00068). Hence, we find that the association between AMD and elevated NLR may have stronger relevance to the neovascular subtype of AMD. However, the clinical value of measuring the NLR remains unclear., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The objective of our study was to analyze the prognostic value of the combination of serum ALP and pleural effusion LDH (AL score) for malignant pleural effusion (MPE) patients. Methods: This study includes retrospective, descriptive and observational research from 1 June 2006 to 1 December 2017, which aimed to identify prognostic factors related to MPE patients. We analyzed the association of various clinical features, routinely tested markers from peripheral blood and MPE at diagnosis and overall survival (OS). All MPE patients were assigned to three groups according to their AL score. The impact of the AL score and other prognostic factors were evaluated with multivariable regression. Results: According to their AL score, 193 patients were assigned to three groups with 25 in group 0 (sALP < 65 U/L and pLDH < 155 U/L), 121 in group 1 (sALP > 65 U/L or pLDH > 155 U/L) and 47 (sALP > 65 U/L and pLDH > 155 U/L) in group 2. For groups 0, 1 and 2, median survival times (MST) were 23, 15 and 7 months, respectively. Among the three groups, MST, serum albumin level, C reactive protein, erythrocyte sedimentation rate, the ratios of platelet‐to‐lymphocyte, neutrophil‐to‐lymphocyte showed significant differences. The counts of neutrophils, monocytes, platelets and AL score (0 vs. 1, P = 0.038, hazard ratio [HR]: 1.858, 95% confidence interval [CI]: [1.034, 3.339]; 0 vs. 2, P = 0.001, HR: 2.993, 95% CI: [1.556, 5.531]) were independent prognostic indicators for OS of MPE patients. Conclusion: AL score is a promising indicator which can be used to predict the prognosis of MPE patients. It can assist physicians in the selection of patients for appropriate palliative treatment. Key points: To our knowledge, this paper is the first study that combined two enzymes (sALP and pLDH) from serum and pleural effusion and studied the prognostic value for MPE patients. It has been proved to be a promising indicator to assist physicians select patients for appropriate palliative treatment. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Zand Irani et al paper. To view this article, visit https://doi.org/10.1111/apt.16630 [ABSTRACT FROM AUTHOR]

The first paper in this series reported that it was possible to reconstitute the response of low concentrations of mouse spleen lymphocytes to concanavalin A (Con A) by adding small numbers of peritoneal exudate cells (PEC) to the cultures. In this paper it is shown that the role of the PEC in this system can be partially replaced by conditioned medium (CM) prepared from PEC cultures or completely replaced by CM taken from lymphocytes cultured at optimal concentration. These CM were inactive unless fresh Con A was added to the assay cultures. Activity was present in CM which was incubated with lymphocytes or PEC for the shortest possible time but maximal activity was found after 24 hr of incubation. Activity was also found in CM prepared in the absence of Con A. Only in the case of lymphocytes cultured at optimal concentration for 24 hr was there substantially more activity in the CM thus prepared if Con A was present. PEC preparations depleted of T lymphocytes produced as much activity in CM as the untreated control. CM produced by PEC was less sensitive to heat treatment or to freezing and thawing than that produced by lymphocyte cultures. [ABSTRACT FROM AUTHOR]

Canine transmissible venereal tumour (CTVT) is a naturally occurring contagious neoplasm of dogs located mainly on the external genitalia of both sexes. The course of vincristine chemotherapy, the most effective and practical therapy, is affected by the immune status of the host. The aim was to investigate recombinant human interferon alpha‐2a (rhIFNα‐2a) and vincristine for treatment of CTVT. A total of 21 female dogs were included. In group I (n = 9), vincristine (0.025 mg/kg, IV) was administered weekly. In group II (n = 6), dogs were injected intratumorally weekly with 1.5 million IU rhIFNα‐2a. In group III (n = 6), rhIFNα‐2a and vincristine were combined. No tumour regression was observed after three injections of rhIFNα‐2a in group II and weekly vincristine was administered. The number of tumour infiltrating lymphocytes (TILs), mitotic figures and apoptotic cells were counted in subsequent incisional tumour biopsies. The Kaplan–Meier Method was used to analyse survival using complete tumour regression as the outcome and Breslow Test was used for comparison of survival curves. Differences in TILs, cell proliferation and apoptosis between groups were assessed by analysis of covariance. Complete regression was observed in all animals included. Mean duration of vincristine treatment for complete regression was shorter in group II (3.50 weeks, 95% CI, 3.06–3.94, P < 0.05) and group III (3.17 weeks, 95% CI, 2.84–3.49, P < 0.01) compared to group I (5.11 weeks, 95% CI, 4.42–5.80). Vincristine and rhIFNα‐2a combination increased TILs in CTVT biopsies compared to vincristine treatment (P = 0.017) and vincristine treatment after rhIFNα‐2a (P = 0.049). Vincristine treatment after rhIFNα‐2a (Group II; P < 0.001) and rhIFNα‐2a and vincristine combination (Group III; P < 0.001) decreased apoptosis. The results indicate that intratumoral rhIFNα‐2a treatment alone is not effective in CTVT. However, combination of rhIFNα‐2a and vincristine shortens the duration of treatment compared to vincristine therapy. In this paper, it was found that intratumoral recombinant human IFNα‐2a treatment alone is not effective in canine transmissible venereal tumour. However, combination of recombinant human IFNα‐2a and vincristine shortens the duration of treatment compared to vincristine therapy. [ABSTRACT FROM AUTHOR]

In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published a seminal paper in Immunology entitled ‘Infectious Immunological Tolerance’ 1 indicating that such negative regulation could be a dominant effect that prevented otherwise ‘helpful’ T cells from mediating their function. Over the next decade, suppressor T cells, as these negative regulatory cells became known, were intensively investigated and a complex set of interacting cells and soluble factors were described as mediators in this process of immune regulation. In the early 1980s, however, biochemical and molecular experiments raised questions about the interpretation of the earlier studies, and within a few years, the term ‘suppressor T cell’ had all but disappeared from prominence and research on this phenomenon was held in poor esteem. While this was happening, new studies appeared suggesting that a subset of T cells played a critical role in preventing autoimmunity. These T cells, eventually dubbed ‘regulatory T cells’, have become a major focus of modern cellular immunological investigation, with a predominance that perhaps eclipses even that seen in the earlier period of suppressor T cell ascendancy. This brief review summarizes the rise and fall of ‘suppressorology’ and the possibility that Tregs are a modern rediscovery of suppressor T cells made convincing by more robust models for their study and better reagents for their identification and analysis. [ABSTRACT FROM AUTHOR]

Objective The aim of the research paper was to assess selected laboratory results in children with fever without seizures and febrile seizure. Materials and Methods The paper presents an analysis of a group of 306 children aged 6 months - 5 years who were admitted with diagnosed fever without seizures and febrile seizures in Specialized Health Care Centre for Mother and Child in Poznan between 1st January 2008 and 31st December 2009. Out of the diagnostics procedures performed in children the following ones were taken into consideration: BCC and CRP. Results Of the analyzed group of 306 children, 59.48% were boys and 40.52% were girls. In the studied group 61.93% were boys and control group 56.15% were boys. Mean age of admitted children was 22 months. In the study group mean body temperature was 39.0°C and in the control group 38.6°C. A statistically significant difference was found between body temperature of study and control group ( p = .005). The mean C-reactive protein level in the study group was 15.73 mg/L and in the control group 58.20 mg/L. There was a statistically significant difference ( p < .001). There was a statistically significant difference between the number of lymphocytes and neutrophils ( p < .001). There was also a statistically significant difference between the number of hemoglobin, hematocrit and platelets. Conclusions The study showed that children with FS, had statistically significant higher neutrophils level compared to those with fever without seizures. The number of lymphocytes was lower in children with FS than in children with fever without seizures. [ABSTRACT FROM AUTHOR]

As described in an accompanying paper, trinitrophenyl (TNP) modification of pork insulin (PI) at the A1 glycine position allows this molecule to stimulate a proliferative response in H-2b (B10) mice. We now show that this antigen stimulates low IgG responses in the same strain of mice. Our results show that T-cell help and proliferation may therefore be regulated independently. [ABSTRACT FROM AUTHOR]

T-colony formation can be induced in PHA-stimulated peripheral blood mononuclear cells (PBM) from man, but not in PHA-stimulated purified T cells, the latter requiring the presence of factors produced by PHA-stimulated PBM and termed T-colony promoting activity (TCPA). In this paper, we demonstrate that interleukin-2 (IL-2), the growth hormone of T lymphocytes, controls T-colony formation. We show that: (i) IL-2 activity and TCPA produced by PHA-activated PBM are co-purified by gel filtration and chromatography on blue agarose, a procedure which yields a 850-fold IL-2 purification; (ii) recombinant IL-2, produced by genetically manipulated Eseherichia coli, can induce T-colony formation in PHA-stimulated purified T cells; (iii) Monoclonal antibody against the IL-2 receptor (anti-Tac antibody) completely inhibits the T-colony formation in PHA-stimulated PBM when directly added to the culture system. [ABSTRACT FROM AUTHOR]

Our earlier observations indicate that adoptive transfer of spleen cells obtained from dengue type 2 virus (DV)-primed mice suppressed DV antigen-specific antibody secretion as detected by Jerne PFC technique. Findings of this paper indicate that the suppression was produced by non-glass-adherent cells, macrophage-depleted (by carbonyl iron) cells and by T lymphocytes of the spleen but not by the glass-adherent cells and B lymphocytes. The activity of these cells is dependent upon production of prostaglandin as shown by abrogation of their suppressor activity by pre-treatment of cells by indomethacin or aspirin which are known to block synthesis of prostaglandins. [ABSTRACT FROM AUTHOR]

Background: The relationship between epinephrine and cancer can be dose‐dependent in in vivo study. Whether it is the same in human body still needs verification. Method: We used frozen human pancreatic ductal adenocarcinoma (PDAC) tissues to detect epinephrine content and analyzed its relationship with survival using the K‐M method and Cox regression. Disturbance of blood cell count and C‐reactive protein and identification of related potent intermediary factors were also analyzed. Results: K‐M plot and Cox regression all showed the inverted U‐shaped relationship between epinephrine and PDAC survival. Lymphocyte adjustment can increase the HRs of epinephrine for PDAC death by >10%. Conclusion: Epinephrine played an anti‐tumor or pro‐tumor effect depending on the specific concentration. Circulating lymphocyte count was elevated and might acted as a compensation pathway to reduce the pro‐tumor effect of epinephrine to PDAC. [ABSTRACT FROM AUTHOR]

Background: High neutrophil/lymphocyte ratio (NLR) is associated with poor prognosis in ischemic stroke. However, the role of NLR in cerebral small vessel disease (CSVD) is controversial. Herein, we evaluated the value of NLR in identifying CSVD and its relationship with the common imaging markers of CSVD. Methods: A total of 667 patients were enrolled in this study, including 368 in the CSVD group and 299 in the non‐CSVD group. Clinical, laboratory, and imaging data were collected. The relationship of NLR with CSVD and common imaging markers of CSVD were analyzed with univariate and multivariate logistic regression analysis. The predictive value of NLR was assessed with the receiver operating characteristic curve. Results: NLR (odds ratio [OR] = 1.929, 95% confidence interval [CI] = 1.599–2.327, p <.001) was an independent risk factor for CSVD. NLR was also independently associated with moderate to severe white matter hyperintensity (WMH) (OR = 2.136, 95% CI = 1.768–2.580, p <.001), moderate to severe periventricular WMH (OR = 2.138, 95% CI = 1.771–2.579, p <.001), and moderate to severe deep WMH (OR = 1.654, 95% CI = 1.438–1.902, p <.001), moderately to severely enlarged perivascular spaces (EPVS) (OR = 1.248, 95% CI = 1.110–1.402, p <.001), moderately to severely EPVS in the basal ganglia (OR = 1.136, 95% CI = 1.012–1.275, p =.030), and moderately to severely EPVS in the centrum semiovale (OR = 1.140, 95% CI = 1.027–1.266, p =.014). However, NLR was not statistically significantly associated with lacune. The optimal cutoff point of NLR in predicting CSVD was 2.47, with sensitivity and specificity of 84.2% and 66.9%, respectively (p <.01). The diagnostic effect was maximized when NLR was combined with other risk factors. Conclusions: NLR is an independent risk factor for CSVD and is independently associated with common imaging markers of CSVD. NLR may serve as a valid and convenient biomarker for assessing CSVD. [ABSTRACT FROM AUTHOR]

Background: Feline large granular lymphocyte (LGL) lymphoma is an aggressive neoplasia characterised by short survival and poor response to chemotherapy. Objectives: In this study, the effect of different chemotherapeutic agents on the growth kinetics of the feline cell line S87, a non‐MHC‐restricted feline LGL cell line, was investigated. Where possible, IC50 (inhibitory concentration 50) values were determined. The IC50 values of the cell line as lymphoma models can provide clues to the situation in vivo and serve as a basis for studying resistance mechanisms. Methods: Cells were incubated with various concentrations of vincristine, doxorubicin, 4‐hydroperoxycyclophosphamide, prednisolone, methotrexate and L‐asparaginase for 24 and 48 h, respectively. Results: The IC50 values could be determined as 14.57 (7.49–28.32) μg/mL at 24 h incubation and 5.72 (4.05–8.07) μg/mL at 48 h incubation for doxorubicin and 9.12 (7.72–10.76) μg/mL at 24 h incubation and 4.53 (3.74–5.47) μg/mL at 48 h incubation for 4‐hydroperpoxycyclophosphamide. Treatment with vincristine and methotrexate resulted in relatively high cell resistance whereas L‐asparaginase and prednisolone treatment led to a reduction in cell number compared to control while cell viability was not affected (cytostatic effect). Conclusion: Overall, the feline LGL cell line S87 proves to be relatively sensitive to doxorubicin and 4‐hydroperoxycyclophosphamide and relatively resistant to treatment with vincristine, prednisolone, methotrexate and L‐asparaginase. The results of this study can be used for further investigations on resistance mechanisms in feline LGL lymphoma. Doxorubicin and cyclophosphamide can be interpreted as promising candidates for the therapy of feline LGL lymphomas. [ABSTRACT FROM AUTHOR]

The cellular and molecular mechanisms involved in many abnormalities described in Systemic Lupus Erythematosus (SLE) are still unclear. Some of these abnormalities referred to the hyperactivation of T lymphocytes and the enhanced secretion of MMP-9 by peripheral blood mononuclear cells (PBMCs). Therefore, in this paper we investigated the potential role of CD147 molecule in these abnormalities. Our results demonstrated that CD147 molecule is overexpressed on CD3+T lymphocytes from SLE patients when compared with CD3+T lymphocytes from healthy donors. Monoclonal anti-CD147 antibodies, MEM-M6/1 clone, were able to inhibit protein tyrosine phosphorylation only in CD3 X CD28 costimulated T lymphocytes from SLE patients. However, this monoclonal antibody was unable to inhibit the enhanced activity of MMP-9 secreted by SLE PBMCs. [ABSTRACT FROM AUTHOR]

The article presents information about abstracts of various papers that will be discussed at the Discussion Group of the 6th European Congress on Epileptology that will be held on June 1, 2004. One of the papers that will be discussed is "Cytokines and Acute Neurodegeneration in CNS Disorders," by S. Allan. Cytokines are a large and varied group of immune molecules that have diverse actions in the brain, including a key role as mediators of acute neurodegeneration. Other papers that will be discussed are "The Role of the Interleukins in Febrile Seizures," by R. Straussberg and "The Significance of Cytokine Production in Clinical Epilepsy," by J. Peltola and K.A. Lehtimaki.

Summary Secondary lymphoid tissue consists of two major populations of cells: lymphoid cells and stromal cells. It is generally accepted that these two cell populations influence each other however, factors mediating these processes are poorly understood. In this paper we characterize one of the possible means of communication between stroma and lymphocytes namely through hepatocyte growth factor/c-met receptor interactions. Hepatocyte growth factor (HGF) is a pleiotropic factor that is mainly produced by mesenchymal cells and acts on cells of epithelial origin which express the HGF receptor c-met. Here we demonstrate that biologically active HGF is constitutively produced by fibroblast-like stromal cells from human lymphoid tissues. HGF secretion from stromal cells was increased by direct contact with activated T cells. This increase was abrogated when activated T cells were separated physically from stromal cells. Using neutralizing antibody or cytokine inhibitors we provide evidence that enhancement of HGF production was due to additive effects of T-cell membrane-associated interleukin-1 (IL-1) and CD40 ligand. Finally, we also show that B lymphocytes activated with CD40L/anti-µ or phorbol 12-myristate 13-acetate (PMA) express c-met receptor. Co-culture of activated B cells with stromal cells from spleen leads to enhanced production of immunoglobulins. This can be partially inhibited by introduction of anti-HGF neutralizing antibodies to the culture system. Substitution of stromal cells with recombinant HGF did not produce enhancement of immunoglobulin secretion. On the other hand stimulation of c-met receptor with HGF leads to enhanced integrin-mediated adhesion of activated B cells to vascular cell adhesion molecule (VCAM-1) and fibronectin. On the basis of the above experiments we conclude that HGF production by fibroblast-like stromal cells can be modulated by activated T cells, thus providing signals for the regulation of adhesion of c-met expressing B cells to extracellular matrix proteins. In this way HGF may indirectly influence immunoglobulin secretion by B cells. [ABSTRACT FROM AUTHOR]

Background: Thymic epithelial tumors (TET) are rare malignancies and lack well‐defined biomarkers for neoadjuvant therapy. This study aimed to evaluate the clinical utility of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in TET. Methods: Patients initially diagnosed with unresectable thymoma or thymic carcinoma who underwent neoadjuvant therapy between January 2004 and December 2021 formed our study population. Hematoxylin and eosin‐stained sections from the initial biopsy and surgery were analyzed using an AI‐powered spatial TIL analyzer. Intratumoral TIL (iTIL) and stromal TIL (sTIL) were quantified and their immune phenotype (IP) was identified. Results: Thirty‐five patients were included in this study. The proportion of patients with partial response to neoadjuvant therapy was higher in the group with nondesert IP in preneoadjuvant biopsy (63.6% vs. 17.6%, p = 0.038). A significant increase in both iTIL (median 22.18/mm2 vs. 340.69/mm2, p < 0.001) and sTIL (median 175.19/mm2 vs. 531.02/mm2, p = 0.004) was observed after neoadjuvant therapy. Patients with higher iTIL (>147/mm2) exhibited longer disease‐free survival (median, 29 months vs. 12 months, p = 0.009) and overall survival (OS) (median, 62 months vs. 45 months, p = 0.002). Patients with higher sTIL (>232.1/mm2) exhibited longer OS (median 62 months vs. 30 months, p = 0.021). Conclusions: Nondesert IP in initial biopsy was associated with a better response to neoadjuvant therapy. Increased infiltration of both iTIL and sTIL in surgical specimens were associated with longer OS in patients with TET who underwent resection followed by neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Nutritional availability during fasting and refeeding affects the temporal redistribution of lymphoid and myeloid immune cells among the circulating and tissue‐resident pools. Conversely, nutritional imbalance and impaired glucose metabolism are associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent immune cell function and trafficking are scanty. Here, we report that oral glucose load in mice and healthy men enhances the adherence of circulating peripheral blood mononuclear cells (PBMCs) and lymphocytes to fibronectin. Adherence to fibronectin is also observed upon regular intake of breakfast following overnight fasting in healthy subjects. This glucose load‐induced phenomenon is abrogated in streptozotocin‐injected mice that lack insulin. Intra‐vital microscopy in mice demonstrated that oral glucose feeding enhances the homing of PBMCs to injured blood vessels in vivo. Furthermore, employing flow cytometry, Western blotting and adhesion assays for PBMCs and Jurkat‐T cells, we elucidate that insulin enhances fibronectin adherence of quiescent lymphocytes through non‐canonical signalling involving insulin‐like growth factor‐1 receptor (IGF‐1R) autophosphorylation, phospholipase C gamma‐1 (PLCγ‐1) Tyr783 phosphorylation and inside‐out activation of β‐integrins respectively. Our findings uncover the physiological relevance of post‐prandial insulin spikes in regulating the adherence and trafficking of circulating quiescent T‐cells through fibronectin–integrin interaction. [ABSTRACT FROM AUTHOR]

Gamma inferferon (gamma IFN), alpha tumor necrosis factor (alpha TNF), and interleukin 6 (IL-60) are cytokines produced by a wide variety of cells, including T lymphocytes and NK cells. These cytokines affect B-cell proliferation and differentiation into immunoglobulin secreting cells. In addition, gamma IFN and alpha TNF also enhance the function of macrophages, upregulating the expression of their IgG receptors. Abnormalities in the production of these cytokines may be involved in the clinical course of autoimmune thrombocytopenic purpura (ATP). This paper describes the production of these cytokines in PHA-stimulated peripheral blood CD2+ cells from ATP patients. Both gamma IFN and alpha TNF were significantly increased in PHA-stimulated CD2+ cells from therapy-dependent ATP patients (platelet counts < 50,000/microliter), as compared to ATP patients with stable disease (sustained platelet counts < 50,000/microliter without need treatment) (P < 0.05). No significant differences were found in gamma IFN production by PHA-stimulated CD2+ cells between therapy-dependent ATP patients and healthy controls (P < 0.05). However, the production of alpha TNF by PHA-stimulated CD2+ cells from therapy-dependent ATP patients was significantly higher compared to that found in healthy controls (P < 0.05). There were no significant differences in IL-6 production by PHA-stimulated CD2+ cells from ATP patients and healthy controls (P < 0.05). These findings demonstrate abnormal gamma IFN and alpha TNF secretion in purified CD2 cells from ATP patients. The clinical severity of the disease is associated with the altered secretion of these lymphokines by CD2 cells.

Cells of the B-cell lineage play an essential part in the immune response, not only as the producers of antigen-specific antibodies, but also as antigen-presenting cells. Unlike T cells, however, the establishment of long-term normal B-cell lines has proved to be exceedingly difficult. In this paper we demonstrate that cell membrane-expressed CD154 (CD40 ligand) is able to support the continual growth of porcine mesenteric lymph node B-cell cultures for more than 4 months without the addition of exogenous cytokines, such as interleukin-4 (IL-4). Addition of IL-4, but not interferon-γ (IFN-γ) or IL-13, to these cultures enhanced proliferation, as, to a lesser extent, did addition of IL-2. Interestingly, however, whilst IFN-γ-supplemented cultures largely consisted of immunoglobulin M (IgM)-positive cells, cultures with IL-13 or IL-4 contained a significantly increased proportion of IgG-positive cells. [ABSTRACT FROM AUTHOR]

As part of our current efforts to develop assays and reagents to study the immune system of marine mammals, and in view of the effort currently made to develop monoclonal antibodies to cell surface proteins of lymphocyte subsets in different species, the present paper reports on the characterization of a monoclonal antibody against the homologue of CD45R on cetacean lymphocytes. The specificity of this antibody has been characterized on the basis of immunoprecipitation of the antigen it recognized, immunoperoxidase staining on cetacean lymph node and thymus sections, as well as one and two-colour flow cytometric analysis of cetacean peripheral blood mononuclear cells and single-cell suspensions of thymus, lymph node and spleen. Anti-cetacean CD45R (F21.H) immunoprecipitated proteins of 180, 200 and 220×103 MW, with the 180×103 MW form being predominantly expressed on T cells and the 220×103 MW form expressed predominantly on B cells and thymocytes. F21.H labelled all B cells and a proportion of T cells on single-cell suspensions of spleen cells. CD45R- killer whale peripheral blood lymphocytes expressed a higher density of CD2 than CD45R+, a characteristic of memory T cells. Killer whale T lymphocytes also lost the expression of CD45R upon activation with concanavalin A (Con A) and phytohaemagglutinin (PHA). This is the first report of a monoclonal antibody to CD45R in cetaceans, and this antibody is foreseen as a possible valuable diagnostic and research tool to assess immune functions of captive and wild cetaceans as part of the evaluation of their health status. [ABSTRACT FROM AUTHOR]

Alveolar macrophages (AM) are recognized as archetypal ‘activated’ macrophages with respect to their capacity to suppress T-cell responses to antigen or mitogen, and this function has been ascribed an important role in the maintenance of local immunological homeostasis at the delicate blood: air interface. The present study demonstrates that this suppression involves a unique form of T-cell anergy, in which ‘AM-suppressed’ T cells proceed normally through virtually all phases of the activation sequence including Ca2+ flux, T-cell receptor (TCR) modulation, cytokine [including interleukin-2 (IL-2)] secretion and IL-2 receptor (IL-2R) expression. However, the ‘suppressed’ T cells fail to up-regulate CD2, and do not re-express normal levels of TCR-associated molecules after initial down-modulation; moreover, they are unable to transduce IL-2 signals leading to phosphorylation of IL-2R-associated proteins, and remained locked in G0/G1. The induction of this form of anergy is blocked by an NO-synthase inhibitor, and is reversible upon removal of AM from the T cells, which then proliferate in the absence of further stimulation. We hypothesize that this mechanism provides the means to limit the magnitude of local immune responses in this fragile tissue microenvironment, while preserving the capacity for generation of immunological memory against locally encountered antigens via clonal expansion of activated T cells after their subsequent migration to regional lymphoid organs. In an accompanying paper, we demonstrate that a significant proportion of T cells freshly isolated from lung exhibit a comparable surface phenotype. [ABSTRACT FROM AUTHOR]

Peripheral lung tissue contains large numbers of T cells, strategically located for immune surveillance at the blood-air interface. Given the intensity of antigenic exposure at this site, it is clear that local T-cell activation events require strict control, in order to maintain tissue homeostasis. How this control is achieved in this unique tissue microenvironment is unknown, and the present study sought to elucidate the process via detailed analysis of the surface phenotypic characteristics of freshly isolated lung T cells. We report below that these cells display typical characteristic of ‘postactivation’, notably elevated basal Ca2+ concentrations, down-modulated T-cell receptors, expression of Ia and ‘late’ activation antigens and concomitant CD4/CD8. However, levels of interleukin-2 receptor and CD2 expression were below those expected of ‘activated’ T-cell populations, and virtually all of the cells were found to be in the G0/G1 phases of the cell cycle. These properties bear a remarkable similarity to those of T cells activated in the presence of endogenous tissue (alveolar) macrophages from the lung (see accompanying paper). We hypothesize that they reflect the in vivo operation of an endogenous macrophage-mediated T-cell anergy-induction process, the function of which is to limit the local clonal expansion of T cells in peripheral lung tissue after in situ activation. [ABSTRACT FROM AUTHOR]

This paper describes a model for investigation of the functional implications of B-cell activation for antigen presentation. Mixed lymphocyte cultures were used to assess the ability of freshly isolated B cells, mitogen-activated B cells and Epstein Burr virus (EBV)-transformed B-cell lines to stimulate the activation and proliferation of allogeneic T cells under a variety of experimental conditions. It was found that resting B cells presented antigen poorly, while activated cells were highly immunogenic. Paraformaldehyde fixation completely eliminated antigen presentation by resting B cells, despite constitutive expression of class II MHC antigens. However, fixation had little effect on antigen presentation by activated B cells that expressed B7-1 and B7-2 in addition to class II major histocompatibility complex (MHC) molecules. Arrest of B-cell activation by serial fixation after treatment with F(ab′)2 fragments of goat anti-human IgM produced cells with variable antigen-presenting capacity. Optimal antigen presentation was observed for cells fixed 72hr after the initiation of B-cell activation. Although both BT-1 and B7-2 antigen expression increased after B-cell activation, it was found that the rate of T-cell proliferation correlated most closely with B7-2 expression. Stimulation of T cells by fixed activated B lymphocytes could be blocked by antibodies directed at class II MHC molecules, indicating involvement of the T-cell antigen receptor. In addition, T-cell proliferation was inhibited by antibodies specific for B7-1 and B7-2 and by the fusion protein CTLA4-Ig, demonstrating a requirement for CD28 signal transduction. The sole requirement of B7 family expression for antigen presentation by B lymphocytes was shown by demonstration of T-cell stimulation by fixed resting B cells in the presence of CD28 antibody as a source of artificial costimulation. [ABSTRACT FROM AUTHOR]

A receptor which binds secretory lgA (sIgA) is expressed on human T cells from patients with systemic lupus erythematosus, rheumatoid arthritis, Behcet's syndrome and IgA nephropathy and on normal T cells following phytohaemagglutinin (PHA) stimulation. The specificity of this receptor was initially probed with a panel of normal serum immunoglobulins in competitive inhibition assays with sIgA using two-colour immunofluorescence. While the receptor showed the strongest affinity for igAl (IC5010-6 M), IgD which has a similarly glycosylated hinge region to IgAl, also bound to the receptor (IC50 10-5 M). IgA2, which lacks the 'O'-glycosylated hinge region, did not significantly inhibit the binding at these concentrations suggesting that the IgA determinants for this receptor might be the oligosaccharides present in the hinge region of IgAl. IgAl has up to 10 'O'-linked oligosaccharides and four N-linked oligosaccharides per molecule. In order to probe the role of the 'O'-linked hinge sugars in the binding event, a sugar library was prepared from IgAl by a procedure designed to release 'O'-linked oligosaccharides preferentially, and to retain them in the natural closed ring formation. The sugars were released by hydrazinolysis at 65° and the resulting oligosaccharide library analysed by high voltage paper electrophoresis (HVE) and P4 gel permeation chromatography. Competitive inhibition studies demonstrated that both the library and the individual 'O'-linked sugars associated with IgA1 were implicated in the binding of IgAl to this receptor (IC50 between 1 × 10-5 M and 6 × 10-s M). Within this range the individual sugars showed small differences in their affinity for the receptor in the following order: Galβ3GalNAc = NeuNAc2α3(6)Galβ3GalNAc > NeuNAc2α3(6)Galβ3[NeuNAc2α6]GalNAc ≥ GalNAc. [ABSTRACT FROM AUTHOR]

Mononuclear cell migration across the endothelium and through connective tissue into inflammatory sites is a multi-step process. After adhesion to the endothelium, there is an initial change in shape from spherical to irregular, followed by the migratory phase itself in which the cells constantly change in shape. In this paper we have investigated the possibility that the shape-changing in this latter phase is controlled by serine/threonine phosphorylation. For this purpose, we used a spontaneously shape- changing variant of U937 monocytoid cells as well as human peripheral blood lymphocytes that had been previously activated by anti-CD3. To test the role o f phosphorylation in shape-changing, a wide range of serine/threonine kinase inhibitors was tested, including ML-7, KT5720, KT5823, H7, H8, staurosporine, calphostin C, sphingosine, bisindolylmaleimide, chelerythrine and KN-62. Only those compounds which inhibited protein kinase C prevented lymphocyte and U937 shape-change and transmigration across polycarbonate filters. However, one specific protein kinase C inhibitor, bisindolylmaleimide, stimulated lymphocyte shape-change, [n conclusion, these studies show that activation of a serine/threonine kinase is necessary for the constant shape-changing required for motility of mononuclear cells. The kinase may be a protein kinase C isotype or a closely related enzyme. [ABSTRACT FROM AUTHOR]

Lectins can be used to detect changes in cell-surface glycosylation. In this paper we examine the lectin-binding characteristics of murine T cells as measured by flow cytometry. A large panel of labelled lectins was used to stain naive, activated and resting murine T cells. Some lectins did not detectably bind any T cells, some bound to all T cells and some bound to only a subset of splenic T cells. Three lectins which preferentially bind to previously activated T cells were identified: Bandeiraea simplicifolia BS-I, Bauhinia purpurea and Lycopersicon esculentum. In addition, two lectins were found to bind preferentially to activated T cells; Glycine max and Triticum vulgaris. Finally, no differences were found in the ability of a large panel of lectins to bind to Th1 and Th2 clones. Lectin binding may be a powerful tool for distinguishing naive, activated and memory T cells. [ABSTRACT FROM AUTHOR]

This paper describes a T-cell targeting strategy based on the use of an antigen-monoclonal antibody heteroconjugate. A rat anti-idiotypic monoclonal antibody specific for a murine B-cell lymphoma was conjugated to the purified protein derivative (PPD) of tuberculin. This construct selectively delivered up to 4.5 &times 104 molecules of PPD onto each tumour cell. Targeted PPD was internalized for endosomal processing and was presented in association with the I-A class II restriction element to PPD-reactive T-helper (Th) cells. Activated Th cells were demonstrated to proliferate and secrete significant levels of tumour necrosis factor (TNF). Such lymphokine secretion was observed at a PPD concentration as low as 1 ng/mI. Despite the secretion of TNF, the S-cell lymphoma was found to be resistant to autonomous Th-mediated cytotoxicity. Targeted Th cells did, however, activate tumourcidal macrophages that subsequently mediated significant tumour cytostasis. Based on this observation, it is proposed that the targeting system described may be exploited as the basis for a future immunotherapeutic strategy. [ABSTRACT FROM AUTHOR]

This paper describes attempts to isolate and characterize glycosaminoglycan (GAG)-binding molecules on the surface of lymphocytes and lymphoma cell lines and relate their expression to splenic and lymph node homing capacity. Initial binding studies with radiolabelled GAG and rosetting studies with GAG-coupled erythrocytes revealed that there are receptors on lymphocytes for the major classes of GAG (i.e. hyaluronic acid, chrondroitin sulfates, heparin), but lymphocytes bind heparin much more avidly than other GAG species. Analysis of the binding of solubilized radiolabelled cell-surface molecules to immobilized GAG revealed cell-type specific expression of GAG-binding molecules. Thus, each of four lymphoma cell lines tested gave a characteristic pattern of GAG-binding molecules, some molecules being unique to a particular cell line and others being shared by some of the lines. Similarly, splenocytes expressed at least 10 distinct GAG-binding molecules with molecular weights (MW) ranging from 10,000 to 100,000, whereas thymocytes expressed additional GAG-binding proteins of 190,000 and 250,000 MW. Furthermore, splenocytes differed from thymocytes by possessing a unique family of cell-surface molecules which reacted with each GAG. Immunoprecipitation studies demonstrated that the GAG-binding molecules on splenocytes did not correspond to any of the cell-surface antigens tested, notably the cell adhesion molecules MEL-14, CD11/CD18 and CD44, although CD8 bound weakly to heparin. Four lymphoma cell lines with well-characterized migration properties were examined for GAG-binding molecules which may control lymphocyte migration. It was found that no one GAG-binding protein could be correlated with the entry of cells into a particular lymphoid organ. Nevertheless, the role of GAG-binding molecules in the subsequent positioning of lymphocytes within lymphoid organs requires further investigation. [ABSTRACT FROM AUTHOR]

The experiments described in this paper have examined the migration of three fluorochrome-labelled T-lymphocyte subsets (CD4+, CD8+ and γδ+T19+) on a single passage from blood to lymph, through prescapular lymph nodes. Lymphocytes obtained from prescapular efferent lymph were labelled in vitro with fluorochrome and returned to the blood of the same animal. Over the next 2 days, lymph was continuously monitored and the cells in all collections, including the one used for intravenous infusion, were phenotyped and analysed by flow cytometry. Significant differences in the subset ratios between the infused, starting population and the recirculated population iodicated that CD4+ and γδ+T19+ lymphocytes are extracted by a resting lymph node at the same rate and that both are extracted at a faster rate than CD8+ lymphocytes. The results presented here also suggest that a unique subset of γδ+T19+ lymphocytes may be present in blood that does not recirculate through peripheral lymph nodes. [ABSTRACT FROM AUTHOR]

The experiments reported in this paper examine the cell-surface phenotype (CD5, CD4, CD8, TI9, MHC class II and sIg) and cell output of lymphocyte subsets circulating through a subcutaneous lymph node in the sheep fetus, in an environment unaffected by foreign antigen and circulating immunoglobulins. CD4+ lymphocytes were the major T-cell subset in fetal lymph and were clearly enriched in lymph compared with blood, whereas TI9+, CD8+ and B lymphocytes were not. It seems likely that in the fetus CD4+ lymphocytes are extracted from the blood at a faster rate than are other T-cell subsets and B cells. There was a much higher percentage of CD8+ and T null cells and a lower percentage of MHC class II+ and B cells circulating in the fetal lymph than in adult lymph, while the percentage of TI9+ lymphocytes in fetal blood was twice that in the adult. Although the hourly cell output from an adult prescapular lymph node was far higher than that from a fetal lymph node, the circulation of lymphocytes through fetal lymph nodes was much greater per gram lymph node weight than that through adult lymph nodes. The wholesale recirculation in the fetus of all the major T-cell subsets found in the adult is paradoxical because it is not known what function they serve in the fetus in the absence of antigen and ongoing immune responses, although clearly they are not memory cells. [ABSTRACT FROM AUTHOR]

Previous studies have shown that lymphocytes carry cell surface receptors for sulphated polysacchar-ides (SPS), and SPS recognition may play a role in lymphocyte migration and positioning in vivo. This paper describes attempts to isolate and characterize the endogenous glycosaminoglycans (GAGs) of murine spleen and determine whether splenic lymphocytes carry cell surface receptors for these GAGS. A procedure was devised for isolating GAGs from murine spleen in good yield and high purity and the GAG preparation was then radiolabelled for subsequent binding studies. It was found that the splenic GAGs bound to murine splenocytes in a saturable, rapid and reversible manner with only a small subpopulation of the splenic GAG preparation being involved in binding. This reactive species was chondroitinase ABC-resistant and nitrous acid-sensitive, indicative of a heparan sulphate/heparin-like molecule. Furthermore, using immunofluorescent flow cytometry studies it was demonstrated that the majority of spleen cells have receptors for these GAGs. Subsequent ion- exchange fractionation and SDS-PAGE analysis of chondroitinase ABC-resistant GAGs confirmed that the splenic GAG recognized by splenocytes was a heparan sulphate/heparin molecule of approximately 20,000 MW with a binding affinity to splenocytes of approximately 5 × 10-8 M. Additional binding inhibition studies indicated two possible binding sites, for splenic GAGs on the splenocyte surface, one being fully inhibited by a range of SPS such as heparin (both coagulant and anticoagulant forms), pentosan sulphate, fucoidan, dextran sulphate, λ- and t-carrageenan, and the second being partially inhibited by κ-carrageenan. The possible relevance of these heparan sulphate! heparin receptors on splenocytes to lymphocyte positioning in vivo is discussed. [ABSTRACT FROM AUTHOR]

The thoracic duct or efferent prescapular duct was cannulated in four fetal calves aged 121-259 days post-conception. The duration of lymph flow ranged from 2 to 20 days and the mean flow rates sustained over these collection periods varied from 54 to 488 ml/hr. Lymphocyte output ranged from 44 × 106 cells/hr in thoracic duct lymph from a 121-day fetus to 3.9 × 108 cells/hr in efferent prescapular lymph from a 259-day fetus. The circulating lymphocyte pool in fetal calves of about 120 and 190 days gestational age was calculated to contain, respectively, 4 × 108 cells and 2 × 1010 cells. The proportion of lymphocytes bearing surface immunoglobulin detected in fetal lymph ranged from 2.1% to 8.7%. Recirculating lymphocytes from fetal calves produced strong proliferative responses when stimulated by T-cell mitogens but responded poorly to B-cell mitogens. Fetal lymphocytes also responded to stimulation by allogeneic cells and stimulated other cells to proliferate during mixed lymphocyte culture. When stimulated with Con A, fetal lymphocytes secreted IL-2 to a degree that was indistinguishable from the secretory behaviour of lymphocytes from adult animals. The results presented in this paper show that chronic lymphatic fistulae can be established successfully in fetal calves to give access to recirculating lymphocytes. This provides a new experimental approach for studying the development of the bovine immune system. [ABSTRACT FROM AUTHOR]

In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24–48 hr after antigen challenge were preceeded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 routine turnout system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngencic turnout system, we have transferred lymph node, spleen lymphocytes and scram from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000–80,000 MW fraction, and a 120,000–190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000–80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. [ABSTRACT FROM AUTHOR]

MRL-+, MRL-lpr and B6-lpr have been shown to be useful models in studying systemic lupus erythematosus. MRL-lpr and B6-lpr differ from their congenic counterparts by the presence and expression of the homozygous recessive lymphoproliferation (Ipr) gene. One manifestation of this gene is a massive Tall proliferation that results in a generalized lymphadenopathy in older animals. A paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigate the basis for this hypo responsiveness in antigen-induced activation of proliferation and antibody synthesis. We have demonstrated that spleen cells from both MRL-+ and MRL-lpr mice gave minimal stimulation in a one-way mixed lymphocyte reaction against allogeneic T cells. These findings were extended to include antigen-specific proliferation involving antigen that must be processed and presented to responder lymphocytes in a H-2 restricted manner. Thus, MRL- + and MRL-lpr spleen cells pulsed with ferredoxin also failed to stimulate ferredoxin-primed T cells from B10.Br animals in vitro. We then investigated whether any T-cell defect(s) was also contributing to this proliferative hyporesponsiveness. T lymphocytes from the spleen of MRL- +, 2-month-old MRL-lpr, and 6-month-old MRL-lpr were tested in a one-way mixed lymphocyte reaction. It was found that only the MRL- + T cells gave responses approaching normal, suggesting lpr gene involvement in T-cell non-responsiveness. This was confirmed by the demonstration of an age-onset T-cell proliferative hyporesponsiveness in B6. lpr mice. This lpr gene-linked non-responsiveness was also shown to extend to T-cell helper function in a positive allogeneic effect assay. We can conclude from these studies that antigenic non-responsiveness in MRL congenic mice can be explained by two defects: (i) the failure of antigen-presenting cells in MRL- + and MRL-lpr mice to provide the necessary signal(s) to immunocompetent T cells, this defect not being associated with the lpr gene, and (ii) the Ip gene controlled outgrowth of a unique T-cell population that cannot respond in our assay systems. [ABSTRACT FROM AUTHOR]

A factor found in the serum of patients with leprosy that inhibits the growth of mitogen-stimulated normal peripheral blood lymphocytes has been studied. The inhibitor, previously identified as an IgG, has been shown to act by blocking the recruitment of lymphocytes into growth. It was not cytotoxic and did not inhibit the rate of growth of those lymphocytes that had been stimulated. The inhibitory activity was less potent if the serum was added after mitogen stimulation. The inhibitor, which could be absorbed by activated but not resting lymphocyte cultures, appeared to act by inhibition of an early event preceding the release of IL-2. The inhibition of mitogen stimulation was overcome by the addition of purified IL-2, although the inhibitor did not block the action of IL-2 on a long-term cultured IL-2-dependent cell line. [ABSTRACT FROM AUTHOR]

Natural killer (NK) activity is inhibited by the contact of peripheral blood lymphocytes with primary monolayer cell cultures of both benign and malignant origin. In this study the effect of interferons (IFNs) on the inhibition has been analysed. Both αIFN- and γIFN-pretreated peripheral blood lymphocytes are effectively inhibited by monolayer target cells. IFN treatment of lymphocytes does not change cytotoxicity against the inhibitory target cells, although it enhances reactivity against NK-sensitive target cells. Treatment of monolayer cells with interferons significantly reduces their inhibitory capacity. However, diminished inhibition of NK activity by the IFN-treated target cells is not associated with increased lysis, probably due to their decreased sensitivity to natural killer cytotoxic factors (NKCF). In 18.5% of the cases studied, monolayer target cells induced endogenous IFN production in lymphocytes. in these cases no inhibition of the NK activity of the effector cells was seen. According to the results of this paper, IFNs have a dual effect on the NK regulatory system: they enhance the NK activity of the effector cells against NK-sensitive target cells, and they change the NK resistant target cells in a way that makes them less inhibitory to NK activity but simultaneously more resistant to the toxic factors secreted by NK cells. [ABSTRACT FROM AUTHOR]

Previous work from this laboratory has shown that preimmunization of syngeneic hosts with Rous sarcoma virus (RSV)-transformed cells elicits a strong immune response against the growth of transplantable RSV sarcomas, mediated by T lymphocytes expressing the surface phenotype of helper cell precursors (Prat, Di Renzo & Comoglio, 1983). This paper shows that anti-tumour immunity may be elicited in tumour-bearing animals by triggering an experimentally pre-amplified T-helper cell population at the site of tumour growth. Mice were treated with cyclophosphamide (which inactivates suppressor T cells) followed by skin sensitization to trinitrochlorobenzene (TNCB) according to a protocol that has been shown to induce an appreciably amplified generation of trinitrophenyl (TNP)-reactive helper T cells (Fujiwara et al., 1984). Five weeks after TNCB painting, mice were transplanted s.c. with a lethal dose of RSV-induced syngeneic sarcoma cells; the injection at the tumour site of TNCB induced the regression of the tumour in mice in which the TNP-helper cell population has been amplified, but not in controls, including those injected with a non-related hapten or sensitized to TNCB without inactivation of suppressors. [ABSTRACT FROM AUTHOR]

In this paper we present experiments that indicate that, in man, most T-celI subpopulations produce interleukin-2 (IL-2), but that the main cell subpopulation which produces it, both upon activation with phytohaemagglutinin or in autologous mixed lymphocyte cultures, is that of autologous rosette-forming (Tar) T4+ T cells. Conversely, the main IL-2-responding T-cell subpopulation is that composed of T cells depleted of Tar (T-Tar) that are T8+ IL-2 was also found to be more effectively produced by Tar cells that do not bind peanut agglutinin (PNA) than by those that do. The PNA T4+ Tar cells were also found to respond best to interleukin- I (IL-I). [ABSTRACT FROM AUTHOR]

This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cyr, ATx5), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5, ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]

This paper describes a method for in vitro measurement of specific cell-mediated immunity in the mouse. Animals were immunized parenterally with ovalbumin in Freund's incomplete or complete adjuvant, and a direct migration inhibition assay was performed, using lymphoid cells from the draining lymph nodes. Migration inhibition was found to be antigen specific, correlated with systemic delayed-type hypersensitivity measured in vivo by skin testing, and had a high degree of sensitivity for ovalbumin. The migrating cells were identified as lymphocytes. Lymph node lymphocyte migration inhibition provides a reliable in vitro assay for regional CMl in the mouse. [ABSTRACT FROM AUTHOR]

In the previous paper we reported that human natural killer (NK) cell activity was augmented greatly by preincubation with Staphylococcus aureus Cowan I bacteria (SpA CoI) or its Protein A. We examined here whether the augmentation with these stimulants is ascribable to the direct activation of NK cells or mediated by some soluble factors produced by the stimulants. It was found that a significant amount of interferon (IFN) was produced by the SpA CoI-stimulation but not by the Protein A-stimulation, although the latter usually induced augmentation of NK-cell activity not less than SpA CoI-stimulation. IFN produced by SpA CoI was considered to belong to α-type IFN, because it was stable at pH 2.0 and could be neutralized effectively by anti-IFNα antibody. Kinetics of NK-cell activation by SpA CoI (but not by Protein A) were very similar to those by IFNα. Furthermore, augmentation of NK-cell activity with SpA CoI-stimulated supernatant was inhibited almost completely by diluted anti-IFNα antibody, whereas augmentation with Protein A-stimulated supernatant could not be abolished by the same treatment. It was, therefore, suggested that augmentation of NK-cell activity with SpA CoI might be ascribable in most part to the IFN induced, whereas Protein A can stimulate NK or T cells directly or soluble factors other than IFN might work as well. [ABSTRACT FROM AUTHOR]