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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.

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]

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.

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]

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]

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]

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]

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]

Sera from mice with large tumours from a variety of tissue types and sources have been shown to contain substances capable of suppressing the proliferative response of normal mouse lymphocytes to concanavalin A (Con A), bacterial endotoxin (LPS) and allogeneic cells. The present paper deals with studies on the nature of these inhibitory materials using mainly a methylcholanthreneinduced rhabdomyosarcoma in DBA/2J mice. It was found that a material responsible for inhibition of the Con A response eluted with immunoglobulins on Sephadex G-150 and eluted with monomeric immunoglobulin on Sephadex G-200. The component of tumour-bearer serum responsible for the suppression of the LPS response of normal lymphocytes eluted from Sephadex G-150 with the α and β globulins and albumin (molecular weight < 150,000). The immunoglobulin-containing serum fraction from tumour-bearing animals inhibited the mixed lymphocyte response, Con A response, and specific immune response to purified protein derivative (PPD) in allogeneic cell systems. It also inhibited the in vitro primary response of mouse cells to sheep red blood cells, and, to a lesser extent, the response to a T cell-independent antigen (DNP-dextran). The inhibitory activity continued to elute with monomeric IgG on Sephadex G-200 when columns were run in 1640 medium and adjusted to pH 2.5, indicating that an acid dissociable complex was not responsible for inhibitory activity. Inhibitor activity could be removed by absorption on immunoadsorbents containing goat anti-mouse immunoglobulin, and could be recovered by acid elution from the adsorbent. Inhibitor activity was not removed by immunoadsorption on columns prepared with antisera to chicken immunoglobulin. [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]

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]

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]

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]

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]

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]

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]

Previous work has established that whereas X/X mice carrying the sex-reversing chromosomal fragment Sxr are positive for the male-specific transplantation antigen, H-Y, X/X mice carrying the variant Sxr', although they too develop as phenotypic males, are H-Y negative. In this paper we show that X/XSxr' male mice do not express any male-specific antigen that can induce skin-graft rejection. [ABSTRACT FROM AUTHOR]