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In a previous paper we described how the toxin ricin stimulates IgE but not IgG antibody responses in rats. In this study we have examined the cellular basis for this observation. The proportion of CD4- and CD8-positive cells present in the spleen at the peak of the IgE response was determined. Those animals injected with both ricin and antigen produced a substantial IgE response (50-fold increase). Their CD4+/CD8+ ratio was also markedly increased (P> 0.001l)compared with animals given toxin or antigen alone. In addition, mitogen-stimulated proliferation of mononuclear cells from spleens of the IgE-producing rats was enhanced nearly five-fold compared with cells from animals given toxin or allergen alone. The sensitivity of CD4- and CD8-positive rat spleen cells from unexposed animals to ricin in vitro was also studied. Spleen cells from untreated rats were co-cultured with optimal doses of mitogen and varying amounts of ricin. Mitogen-driven proliferation was inhibited at l0-3-10-6 mg/ml ricin. This effect was abrogated by the addition of as little as 0.01 m lactose but not by as much as 10 mg/mI mannan to the culture. Cultures depleted of CD4+ cells by rosetting were approximately 100 times more sensitive to ricin (P>0.01). Furthermore, the proportion of CD8 + to CD4+ cells present after culture of untreated cells with mitogen and ricin was significantly reduced. These results show (i) that the ability of ricin to increase the IgE response depends on the administration of antigen together with the toxin; (ii) that CD8+ spleen cells are more sensitive to ricin than CD4 + cells; (iii) that increased IgE responsiveness is associated with a reduction in the proportion of CD8- relative to CD4-positive cells in the spleen and increased responsiveness to mitogen. We believe that enhancement of the IgE responses by ricin may be due to inactivation of IgE-specific T-suppressor cells generated by immunization with antigen and speculate that these may be some or all of those bearing the CD8 marker. [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]

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]

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]

Summary: The circadian clock provides organisms with the ability to track time of day, allowing them to predict and respond to cyclical changes in the external environment. In mammals this clock consists of multiple auto‐regulatory feedback loops generated by a network of circadian clock proteins. This network provides the fundamental basis for rhythms in behaviour and physiology. This clockwork machinery exists in most cells, including those of the immune system. In recent years evidence has emerged highlighting the important role of molecular clocks in dictating the response of immune pathways. While initial work highlighted the effect of the clock in the 'first line of defence', the innate immune system, it has become increasingly apparent that it also plays a role in the more tailored, later‐stage adaptive immune response. This review provides an overview of the role of the circadian cycle in the adaptive immune response. We interrogate the depth of knowledge on cell intrinsic clocks within adaptive immune cells and how these cells may be temporally directed by extrinsic rhythmic signals. We discuss the role of the circadian clock in diseases associated with adaptive immunity such as multiple sclerosis, asthma and parasitic infection. We also discuss the current knowledge on timing of vaccination, and the implications this may have on how we can harness and modulate temporal gating of the adaptive immune response in a clinical setting. [ABSTRACT FROM AUTHOR]

Summary Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important component of the inflammasome, functioning as an adaptor protein that facilitates the recruitment and activation of procaspases that in turn promote the maturation of interleukin-1β (IL-1β) and IL-18. Despite initial focus on the inflammatory properties of ASC there is emerging evidence that highlights the importance of ASC in facilitating adaptive immune responses. However, the cellular and molecular basis for the involvement of ASC in adaptive immunity remains largely unexplored. We have previously demonstrated that activated ASC-deficient T cells have dampened proliferative responses. We have therefore explored the underlying cellular mechanism(s) by which ASC regulates T-cell proliferation. We show that under activating conditions (anti-CD3/CD28 stimulation) in bulk T-cell cultures the presence of ASC−/− CD4+ T cells is sufficient to suppress the proliferative responses of neighbouring T cells. Furthermore, ASC−/− CD4+ T cells upon activation exhibit a suppressive cytokine profile, with elevated production of IL-10 and reduced secretion of T helper type 1 cytokines, interferon-γ and IL-2. This increase in IL-10 secretion within the activated ASC−/− CD4+ T-cell compartment was not associated with a proportional increase in conventional Foxp3+ regulatory T (Treg) cells. Interestingly, when equal numbers of fluorescence-activated cell sorted ASC+/+ and ASC−/− Treg cells (CD4+ CD44intermediate/high CD25+) were activated in vitro, the ASC−/− fraction produced significantly more IL-10 than their wild-type counterparts, suggesting that ASC−/− Treg cells have greater suppressive capacity. Collectively, these results imply that the ASC may influence the development and functioning of Treg cells. [ABSTRACT FROM AUTHOR]

Hepcidin regulates intracellular iron levels by interacting with and promoting the degradation of ferroportin, a membrane protein and the only known cellular iron exporter. Studies of hepcidin expression and regulation have focused on its effects in innate immunity and as a regulator of systemic iron metabolism. In the present study we characterized the expression of hepcidin messenger RNA (mRNA) in human peripheral blood mononuclear cells (PBMCs) with a focus on peripheral blood lymphocytes (PBLs). We found that (1) all human PBMCs analyzed express basal hepcidin mRNA levels; (2) hepcidin mRNA expression increases after T-lymphocyte activation; (3) expression by PBLs increases in response to challenge by holotransferrin (Fe-TF) and by ferric citrate in vitro; (4) the Fe-TF-mediated up-regulation of hepcidin decreases ferroportin expression at the cytoplasmic membrane of PBLs; and (5) silencing of tumour necrosis factor-α (TNF-α) abrogates the effect of Fe-TF. In summary, we show that hepcidin expression determines intracellular iron levels by regulating the expression of ferroportin, as described in other cells, and that inappropriately low expression of hepcidin impairs normal lymphocyte proliferation. The results establish hepcidin as a new player in lymphocyte biology. [ABSTRACT FROM AUTHOR]

Antibodies play an important role in immunity to Salmonella enterica. Here we evaluated the requirement for Fcγ receptors in host resistance to S. enterica using an in vivo model of systemic infection. We show that mice lacking FcγRI, II and III can control and clear a primary infection with S. enterica micro-organisms of low virulence, but are impaired in the expression of vaccine-induced acquired immunity to oral challenge with virulent bacteria. We also show that, in vivo, FcγRI, II, III−/− mice were able to mount efficient T-helper 1 type T-cell responses and antibody responses specific for S. enterica. The work indicates that targeting S. enterica to FcγR is needed for the expression of vaccine-induced acquired immunity, but is not essential for the engenderment of T- and B-cell immunity to the bacterium in vivo. [ABSTRACT FROM AUTHOR]

What controls the fate of the T-cell response remains incompletely defined. Gain of effector function facilitated by costimulation has been thought to be a crucial factor in determining the outcome of the T-cell response, i.e. long-term memory in the presence of costimulation versus tolerance induction in the absence of costimulation. In this study, we show that while costimulation or cognate CD4 helps to promote the acquisition of effector function during the initial phase of the CD8 T-cell response, the fate of effector CD8 T cells is controlled by the duration of subsequent antigenic stimulation. Effector CD8 T cells differentiate into memory cells only after clearance of antigen, whereas in the presence of persistent antigen, effector CD8 T cells are tolerized. Furthermore, protective immunity against tumour cannot develop in the persisting antigen environment. These results suggest that removal of persisting antigen by other means might be a prerequisite for effective immunotherapy in cancer. [ABSTRACT FROM AUTHOR]

A newly developed immunosuppressive drug, FK506 (Fujisawa, Japan) is known to inhibit T-cell immunity. We have evaluated the action of this compound in MRL/lpr mice which develop a severe autoimmune disease. Eight-week-old female MRL/lpr of mice were treated subcutaneously with 2 mg/kg (high dose), 0·8 mg/kg (medium dose), 0·2 mg/kg (low dose) or solvent only (control) six times per week. Survival times of the mice were prolonged in the medium and the high dose treatment groups. The lymph node swelling was dramatically prevented with the high dose treatment. The increasing footpad swelling seemed to be also suppressed with the treatment. FACS analyses of the spleen cells revealed that FKS06 reduced the percentage of double negative T cells (Thy-1.2+, Lyt-2-, L3T4-). Serological studies showed that anti-ssDNA and anti-dsDNA activities were significantly reduced by the high dose treatment, which is different from recent findings with Cyclosporine A. The high dose treatment also suppressed the total amount of IgG, even though the IgG concentration was rather increase by the medium dose treatment. Decreased proteinuria as well as pathological evaluations of the kidneys and lungs indicated that there were marked ameliorations in these organs with the treatment. These results suggest that FKS06 could be potentially used for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

X-irradiated (250 rads) A mice injected with syngeneic trinitrophenylated spleen cells (Syn-TNP-SC) developed syngeneic delayed-type hypersensitivity (Syn-DTH) after footpad challenge with syngeneic concanavalin A-induced lymphoblasts (Syn-Con A blasts), as indicated by footpad swelling and lymph-node proliferation assays. Genetic analysis with different recombinant strains of mouse revealed that the H-2Dd subregion restricts these immunological activities. A small immunogenic entity was isolated from Syn-TNP-SC extract by gel filtration and affinity chromatography with anti-Dd antibody. X-irradiated A mice injected with this antigen also generated inflammatory responses after challenge with Syn-Con A blasts. Analysis of the data obtained from the gel filtration and the affinity chromatography suggest that the Syn-DTH-stimulating antigen is a fragment of the H-Dd heavy chain with a molecular weight (MW) of 5,000 to 10,000. This fragment does not contain TNP molecules or sugar moieties and neither does it express affinity for antibodies against class 11 products. Ltk- cells transfected with the H-2Dd gene also induced Syn-DTH in X-irradiated A mice, while the parent cells failed to stimulate such a response. Taken together these findings indicate that the selection process in the thymus is not absolute and T cells recognizing self-major histocompatibility complex (MHC) products do migrate from this organ to the periphery of the immune system. The possible biological significance of these autoreactive cells is discussed. [ABSTRACT FROM AUTHOR]

The phenotype of T-helper cells conferring protection against Trichinella spiralis (Ts) was studied using adoptive transfer procedures and T-helper cell subsets isolated by monoclonal antibodies. With these techniques OX8- OX22+ and OX8- OX22- T-helper cell populations were isolated from thoracic duct lymph (TDL) of infected rats three-five-fold more concentrated than in unfractionated lymph. The OX8- OX22- cell subset alone transferred enhanced rejection of adult worms from the intestine. The origin of protective OX8- OX22- cells was examined in mesenteric lymphadenectomized (MX) rats. After MX, protective cells were found in the cell population draining directly from the intestine on Days 2-3 after infection. Protective cells first appeared in the mesenteric lymph node (MLN) and efferent lymph at Day 3. MX rats rejected T. spiralis at the same time as intact controls and showed enhanced rejection when immune TDL were transfused. No evidence was found for a direct role of the MLN in the generation or expression of parasite rejection. Depletion of migrating OX8- OX22- blast cells by 48-hr drainage of TDL did not influence the expression of an anamnestic response to challenge infection. This suggests that an intestinally resident cell population has a substantial role in mediating primary worm rejection and anamnestic immunity. Day 2 OX8- OX22- cells from MX rats proliferated in response to the presentation of adult and muscle larvae antigens in vitro. We conclude that protection resides in the OX8- OX22- T-helper cell subset that is produced and functions in the intestine. [ABSTRACT FROM AUTHOR]

A cyclophosphamide (Cy)-resistant immunogenic tumour, the L51I 78Y lymphoma, was used to demonstrate that Cy-treatment of a host bearing this tumour enables passively transferred tumour- sensitized T cells to cause complete tumour regression without any need for Cy to cause a reduction in tumour burden. It was shown that whereas infusion of tumour-sensitized T cells from immune donors had very little effect on growth of the tumour, and whereas treatment with 150 mg/kg of Cy caused appreciable enhancement of tumour growth, combination therapy with Cy plus immune T cells caused complete tumour regression and resulted in long-term survival. Evidence that Cy treatment facilitated the expression of adoptive immunity against the L5178Y lymphoma by eliminating tumour-induced suppressor T cells consisted of the demonstration that tumour regression caused by combination treatment with Cy and immune T cells could be inhibited by infusing the recipient with Cy-sensitive, L3T4+ T cells from tumour-bearing but not from normal donors. [ABSTRACT FROM AUTHOR]

Previous studies of cellular immunity in asymptomatic HBV carriers have been limited to evaluation of responses to plasma-derived HBsAg preparations. We have explored the specificity of cellular immune responses to HBV antigens in these subjects using an indirect T-lymphocyte migration inhibitory factor assay and three antigen preparations (recombinant nucleocapsid antigen (HBcAg), plasma-derived HBsAg with or without pre-S2, and Saccharomyces cerevisiae-synthesized HEsAg without pre-S2 region). T cells from 10 asymptomatic chronic HBV carriers with normal liver function tests were responsive to nucleocapside determinants (mean migration index = 0.55 ± SD 0.07) and to pre-S2-positive plasma-derived HBsAg (MI = 0.62 ± 0.05). However, none responded to HBsAg devoid of pre-S2 sequences (M1=0.98±0.04). In further experiments, T cells from three HBV carriers, cultured with six different HBsAg preparations, exhibited responsiveness only to those preparations containing significant pre-S2 activities. Our results show that T-cell immunity to nucleocapsid determinants of the virus and HBsAg in present in asymptomatic HBV carriers; the latter is restricted to antigenic preparations containing significant pre-S2 activities. Hence, T-cell immunity to pre-S determinants may not always be associated with HBV clearance. [ABSTRACT FROM AUTHOR]

in order to define the antigenic properties necessary for sustained allergic arthritis, we prepared a range of differently charged bovine serum albumin (BSA) species with increasing isoelectric points (4.5, 4.5-7.4, 7-8, 85-9 and >9). The highly cationic BSA >9 appeared to be in a polymeric form. We investigated three properties of these proteins: (i) antigen retention, (ii) T-cell reactivity, and (iii) arthritis induction. Injection of the respective radiolabelled antigens in the knee-joints of immunized mice showed that antigen retention increased with cationicity of the proteins, with the best retention found for ESA with pI>9. However, sustained joint inflammation was only found with BSA859, and not with a level RSA of lower or even higher pI T-cell reactivity in vivo as measured by delayed-type hypersensitivity (skin testing) was similar for the tested antigens, with the exception of polymeric BSA (>9). The latter appeared to be a poor antigen. In vitro, T-cell reactivity ([³H]- thymidine incorporation) against the cationized BSA species was slightly higher as compared to native BSA. The combination of excellent antigen retention and adequate T-cell reactivity appears to be optimal for the induction of chronic arthritis. [ABSTRACT FROM AUTHOR]

Antigen-specific T-helper cells for IgA responses arise in Peyer's patches (PP) following their immunization by subserosal injection of keyhole limpet haemocyanin (KLH). These are of the W3/25 phenotype and the W3/25 receptor is shown here to be involved in their helper function. These cells originate in PP and migrate via mesenteric lymph nodes (MLN) to thoracic duct lymph, although the MLN appear to be unnecessary for the induction or maturation of antigen-specific helper cells collected in thoracic duct lymph after intra-Peyer's patch (i.p.p.) immunization. KLH-specific helper cells can be detected subsequently in the intraepithelial lymphocyte population and also among lamina propria lymphocytes. The helper cells also relocate to PP distant to their site of origin where they are retained only when antigen is present. While i.p.p. immunization is an efficient route for the induction of IgA helper cells in gut-associated lymphoid tissue, it differs from oral immunization in that concomitant induction of antigen-specific splenic suppressor cells does not occur, indicating a role for epithelial antigen processing in this phenomenon. [ABSTRACT FROM AUTHOR]

The mechanism by which a Db-specific helper clone (clone 9) and a hybridoma-derived Db-especific helper factor, referred to as ASHF, induced cytotoxic T lymphocyte (CTL) responses to alloantigens was investigated. Clone 9 or ASHF helped CBA thymocytes to produce CTL against B6 (H-2b), but not D2 (H-2d), alloantigens. However, when BDF1 (H-b,d) spleen cells or an equal mixture of B6 or D2 spleen cells were used as stimulator cells, CTL responses to both B6 and D2 were induced. This suggested that clone 9 cells or ASHF could induce the production of long-ranged, non-antigen-specific helper factor(s) in B6-stimulated cultures. One of these long-ranged factors produced in B6-stimulated cultures was found to be interleukin-2 (IL-2). Thus, clone 9, which is a non-IL-2 producer, increased the production of IL-2 by irradiated B6 spleen cells and by CBA anti-B6 cultures by 4·7- and 5·7-fold, respectively. ASHF did not increase the amount of IL-2 produced by irradiated B6 spleen cells but increased the amount of IL-2 produced in CBA anti-B6 cultures by 3·8-fold. Clone 9 cells or ASHF did not increase IL-2 production in D2-stimulated cultures. Upon stimulation with concanavalin A or antigen, clone 9 cells also produced a non-antigen-specific helper factor. This factor (IL-X) synergized with excess human recombinant IL.2 (rIL-2) in the polyclonal activation of BDF1 or D2 CTL precursors. A model that involves the participation of ASHF, clone 9 cells, IL-2 and IL-X in the induction of a cytotoxic response is proposed. [ABSTRACT FROM AUTHOR]

From our experiments and those of others in which cells were cultured at a density of 100,000 cells per well, it has been suggested that auto antibody production against mouse bromelain-treated erythrocytes (mouse brom-RBC) was independent of T cells, and further, was enhanced by the removal of T cells from responsive cell populations. Here it is shown in limiting dilution cultures that the autoimmune response is highly dependent on T cells or their products. B cells purified from the peritoneal cavities of untreated mice did not differentiate in vitro into autoantibody-secreting cells unless provided with signals from at least one of two types of accessory cells. These were plastic adherent cells and T cells, derived either from the peritoneal cavity or from established cell lines. Here it is shown that peritoneal T cells or T cells from the LBRM-33 cell line stimulated the differentiation of purified B cells in vitro in the absence of added mitogens. The accessory cell effect could be transferred in supernatants derived from T-cell cultures but not filler-cell cultures. Recombinant interleukin-2 (rIL-2) added to culture medium did not stimulate B cells directly, but could increase precursor frequencies when added to unfractionated peritoneal cell cultures, or B-cell cultures to which cells from a T-cell line had been added. From these results, it is concluded that the differentiation of precommitted peritoneal B cells in vitro into autoantibody secretors is at least partially dependent on T cells or lymphokines derived from them. Therefore, any proposed mechanisms for regulation of this autoimmune response should encompass the requirement for T cells or their products in the final differentiation stages to autoantibody secretion. [ABSTRACT FROM AUTHOR]

Characteristics of protective mechanisms during pregnancy were investigated using neonatally thymectomized (NTx) and/or pregnant mice infected with sublethal doses of Listeria monocytogenes, of which the explosive growth at an early phase of 2 or 3 days after infection is prevented by non- immune macrophages, and complete elimination at a late phase from 4 to 10 days after infection is attributed to the augmented functions of macrophages in co-operation with lymphokine-producing sensitized T lymphocytes. Although in virgin control mice there was a gradual decline of bacteria from the day after infection, viable bacteria in pregnant mice showed an increase in number until Day 3. In such pregnant mice, carbon clearance was suppressed. Thus, the enhanced bacterial growth in pregnant mice within 3 days may be attributable to the suppressed functions of non-immune macrophages. Complete elimination of Listeria from Day 4 was observed in pregnant sham-operated mice as well as in non-pregnant and pregnant NTx mice. Twenty-four hour reaction of delayed-type in normal mice induced by sheep red blood cells (SRBC) in incomplete Freund's adjuvant (IFA) was not affected by pregnancy, while 48 hr reaction in mice immunized with SRBC in complete Freund's adjuvant (CFA) was suppressed by pregnancy. We have reported previously that macrophage migration inhibitory factor (MIF) was produced in the latter but not in the former, and that the tuberculin type of delayed hypersensitivity accompanied by MIF production scarcely participated in acquired resistance to Listeria. Effective elimination of Listeria in pregnant and/or NTx mice at a late phase may be attributable to the activity of cellular immunity comparable to 24 hr reaction. These results suggest that T cells showing a low degree of thymus dependency in the ontogenic development may be the major component required for acquired protective immunity against Listeria and may account for the protection in pregnant mice. [ABSTRACT FROM AUTHOR]

This study presents the partial molecular characterization of the alloantigenic rat T-cell marker RT-6. In contrast to most lymphocyte surface membrane proteins, RT-6 proved to be resistant to short- term (15 mm) solubilization by T X-100 at 4°, but could be efficiently solubilized by long-tent (16 hr) exposure at 4° or short-term (15 mm) exposure at 37°. SDS-PAGE analyses of RT-6.2 immunoprecipitates under non-reducing conditions revealed two bands with apparent molecular weights of 21,000 and 24,000 (25,000 and 28,000 under reducing conditions). Radiolabelled sugars failed to be incorporated metabolically into RT-6.2, neither endoglycosidase-F and 0-glycanase digestion nor NaOH treatment caused any detectable decrease in the molecular weight of RT-6.2, and RT-6.2 failed to bind to any of a series of agarose-coupled lectins with a wide range of sugar-binding specificities. These observations suggest that RT-6.2 may lack carbohydrate moieties. [ABSTRACT FROM AUTHOR]

Athymic mice were capable of producing IgM antibodies to B polysaccharide of N. meningitidis when immunized with the polysaccharide complexed to outer membrane proteins, whereas no immunogenicity could be demonstrated with the purified polysaceharide. Transfer of T cells to athymic cells demonstrated that the primary anti-B response was truly thymus-independent but the bulk of the secondary response was thymus-dependent. Transfer of T and B cells purified from spleens of immune mice into irradiated recipients showed the presence of memory T cells, but no memory B cells could be found. [ABSTRACT FROM AUTHOR]

Sex reversed X/X male mice carrying Sxr or the variant Sxr' were typed for expression of the male specific histocompatibility antigen H-Y, by skin grafting and by in vitro cytotoxic and proliferative tests. The X/XSxr males, like X/Y males, were Hey positive by in vitro testing, and failed to reject semiesyngeneic male skin grafts. In contrast X/XSxr' males, like xix females, were H-Y negative and rejected semi-syngeneic, male skin. Spleen cells from X/Y males sensitized C57BL/10 female recipients to reject syngeneic male skin rapidly, whilst immunization with X/X female or X/XSxr' male cells failed to stimulate such second-set responses. These data suggest that the H-Y antigen detected by cytotoxic T cells is the same as that detected by graft rejection responses, that the Sxr' variant is not a tissue-specific regulatory mutation, and that X/XSxr' individuals do not express H-Y antigen but nevertheless develop as phenotypic males. [ABSTRACT FROM AUTHOR]

It has been shown that progressive growth of the P815 mastocytoma in its semisyngeneic B6D2 host results, between days 6 and 9 of tumour growth, in the generation of Ly 1-2+ T cells which are capable, on passive transfer, of causing the regression of an established tumour in γ-irradiated recipients, and of T cells which are capable of lysing P815 tumour cells in vitro. After 9 days of tumour growth, these effector T cells are progressively lost; this is associated with the progressive acquisition of Ly 1+2- suppressor T cells which are capable of inhibiting the expression of passively transferred immunity against an established tumour in T-cell deficient recipients. The results are consistent with the hypothesis that this P815 mastocyroma grows progressively, in spite of its immunogenicity, because it evokes the generation of suppressor T cells before enough effector T cells are generated to reject it. [ABSTRACT FROM AUTHOR]

PPD-reactive T cell clones have been used to analyse the nature of T lymphocytes that are involved in the 'heterogenization' of turnout cells. This is a phenomenon where coupling turnout cells to a strong antigen (in this case PPD) causes an enhanced immune response to tumour-specific antigens to be elicited providing that the host shows T cell immunity to the strong antigen (in this case is BCG positive). Clones of T cells with the Lyt1+ 2- phenotype which were unable to mediate delayed-type hypersensitivity but which provided efficient help to hapten-primed B cells were found to potentiate anti-turnout immunity in BCG-negative syngeneic mice when immunized with Con-A-PPD coupled, X-irradiated MC6A tumour cells. There therefore appears to be a mechanism whereby a helper T cell response to one antigen can provide help for the generation of a T cell response to a linked antigen which is analogous to the well-known phenomenon of help to hapten primed B cells. Furthermore the clones of T cells that help B cells the best are those that give maximal augmentation of T cell immunity. [ABSTRACT FROM AUTHOR]

The ability to resist the facultative intracellular bacterium Listeria monocytogenes was not impaired in the beige mutants of C57BL/6J mice which are known to be deficient in a number of immune functions. The intravenous LD50 of Listeria in beige (bg/bg) mice and their normal heterozygous (bg+) littermates was approximately 5 × 105. Growth of Listeria in the spleen and liver during primary and secondary infections was similar in the two groups of mice, and each was able to act efficiently in adoptive transfer of immunity. Histological examination showed a normal accumulation of polymorphonuclear and mononuclear cells at foci of infection in the liver, while in the spleen the previously described depletion of T cells 2-4 days after infection was observed in both groups. In-vitro 18-hr cytotoxicity of peritoneal cells for P815 targets, a function usually attributed to macrophages, was increased 2 days after infection in both bg/bg and bg/+ mice. In contrast, 4 hr cytotoxicity of spleen cells for YAC-1 targets, considered typical of natural killer (NK) cells, was depressed in uninfected bg/bg mice and only slightly raised during infection. This compared with a normal NK activity in uninfected bg/+ mice which was markedly increased during infection. [ABSTRACT FROM AUTHOR]

Transfer ribonucleic acid (tRNA) was isolated from a two-heptose mutant of Salmonella typhimurium LT2 (strain SL1004) and was found to afford 100% mouse protection against challenge with 1000 LD50 of strain LT2. The intraperitoneal minimum effective dose of tRNA was 5μg RNA per mouse and this dose was significantly lower than that of ribosomal RNA for ddY mouse strain. The protective immunity was independent of the presence of antibodies to cell-surface antigens, and was transferred mainly by T cells. The protective moiety of tRNA was sensitive to ribonuclease digestion which resulted in 85% reduction in the mouse survival rate, but was completely resistant to protease digestion. The present study demonstrates that the immunogenic activity of salmonella RNA is present in both ribosomal RNA and tRNA. [ABSTRACT FROM AUTHOR]

Rat thymus and T-cell antigens were defined by using two distinct monoclonal antibodies (R-1-3B3 and R-1-12CS). R-1-3B3 antibody, when tested for its reactivity with rat lymphoid cells by immunofluorescence, labelled virtually all thymus and T cells but not B cells and bone marrow cells. The antigen defined by this R-1-3B3 antibody occurred more abundantly on medullary thymocytes and peripheral T cells than on cortical thymocytes. Immunochemical data showed that R-1-3B3 antibody recognized a single glycoprotein with a molecular weight of 67,000, which were able to interact with Lens culinaris haemagglutinin. R-1-12C5 antibody, on the other hand, reacted with all of thymus and T cells as well as with a subpopulation (approximately 20%) of bone marrow cells. In contrast to the antigen defined by R-1-3 B3, that detected by R-1-12C5 antibody existed largely on cortical thymocytes and to a much lesser extent on medullary thymocytes and peripheral T cells. R-1-12C5 antibody detected a single glycoprorein with a 95,000 molecular weight, which could also interact with Lens culinaris haemagglutinin. Based on these data described above and since both antigens defined by R-1-3B3 and R-1-12C5 antibodies were absent from rat brain tissue, we concluded that they were distinct from brain-associated thymic antigens in rats including Thy-1 and W3/13 antigen systems. [ABSTRACT FROM AUTHOR]

Inclusion of 14% Ficoll in the assay of rosette formation of human lymphocytes with mouse red blood cells (RBC) markedly enhances the cellular interaction. Both the strength of the rosettes (number of attached RBC) and the number of reacting lymphocytes are increased significantly, irrespective of the lymphocyte source—blood, lymph node and tonsil. In the presence of Ficoll, most of the sIg-bearing B lymphocytes [expressing receptors for Fc(IgG) and/or C3] and a significant number of the sheep RBC-rosetting T lymphocytes (particularly the nylon wool non-adherent subset from the tonsil), express receptors for the mouse erythrocyte. [ABSTRACT FROM AUTHOR]

Cells present in the intestinal lymph of rats were obtained in large numbers by removing the mesenteric, portal and caecal lymph nodes and cannulating the thoracic duct 6 weeks later. About 1% of the cells present in the thoracic duct lymph of these mesenteric lymphadenectomized rats had striking dendritic morphology, were strongly Ia+ but labelled weakly with monoclonal antibodies that recognize rat B or T cells. It was found that intestinal lymph was highly enriched for cells that stimulated allogeneic T cells in the mixed lymphocyte reaction (MLR) and cells with stimulator activity co-purified with dendritic cells. Thus, these dendritic cells appear phenotypically and functionally similar to the dendritic cells that have been described in the mouse spleen and rat lymph node. The ability of the intestinal lymph cells to stimulate rat T cells was used to determine which of the two subsets of these cells were the prime responders in the rat MLR. These subsets, defined by monoclonal antibodies, have been shown by previous work to display close functional analogies to the Lyt 2+ and Lyt 2- subsets in the mouse and to the two human T-cell subsets that have been defined by monoclonal antibodies. It was found that the T-cell subset that contains the helper cells for antibody responses proliferated when irradiated, fully allogeneic or semi-allogeneic thoracic duct cells were used as stimulators, but the subset containing suppressor T cells did so only in the fully allogeneic system. Detailed studies showed that in the absence of helper cells in the responder population T cells in the stimulator population of helper phenotype were responsible for proliferation of the suppressor T-cell subset observed in fully allogeneic MLRs. Proliferation of the suppressor T-cell subset could be obtained using semi-allogeneic stimulators, provided that the Ft cells were derived from a source containing dendritic cells but it was shown that, as in the case with fully allogeneic stimulators, the helper T cells in the stimulator population were playing an active role. These results demonstrate that proliferation of the suppressor T-cell subset in the rat M LR is dependent on blastogenic activity provided by the helper T-cell subset and suggest that in some situations this blastogenic activity may arise through the recognition, by the helper cells, of environmental antigens presented on dendritic cells. It has been reported that in the human MLR both T-cell subsets proliferate but that only the helper subset does so when antigen-primed cells are stimulated with specific antigen. The present experiments, by emphasizing the activity of helper T cells in the stimulator population in the MLR, cast doubt on the implication that recognition of alloantigens in vitro differs in an essential way from that of soluble antigens. [ABSTRACT FROM AUTHOR]

The role of mononuclear phagocyte system (MPS) in the induction of suppressor T cells which depress the delayed footpad reaction to sheep erythrocytes (SR BC) was studied in mice in which MPS was blocked or stimulated. Colloidal carbon and diethyl- stilbestrol were used for blockade and stimulation respectively. Adoptive transfer of suppressor T cells was achieved by spleen cells of mice immunized intra- peritoneally with varying doses of SRBC. In non-treated mice, 1 × 109 SRBC were required to induce suppressor T cells, while 6 × 108 could not induce the suppressor T cells. In MPS-blocked mice, however, even 6 × 108 SRBC could induce the suppressor T cells. On the other hand, 3 × 108 SRBC were required for the induction of suppressor T cells in MPS-stimulated mice. These results suggest that the activity of macrophages as scavenger cells modulates the subsequent induction of suppressor T cells after immunization with high doses of SRBC. [ABSTRACT FROM AUTHOR]

Mice depleted of T cells by adult thymectomy, X-irradiation and reconstitution with syngeneic bone marrow cells, either untreated or treated with anti-Thy-1 serum and complement, were immunized intensively with alum-precipitated bovine serum albumin (AP-BSA) along with or without bacterial lipopolysaccharide (LPS), but no significant anti-BSA antibody response was detected, Priming of the T-cell depleted mice, however, either by a single injection of AP-BSA pins LPS or by multiple injections of AP-BSA without LPS, resulted in the generation of immunological memory. A single injection of AP-BSA without LPS was ineffective. The memory required t he aid of syngeneic T cells to be recalled by the challenge with AP-BSA plus LPS. On the other hand, multiple injections of AP-BSA plus LPS did not cause the generation of memory and the response of these mice to the challenge was lower than that of unprimed control mice. These results suggest that (1) the anti-BSA response is highly dependent on the helper function of T cells, (2) the degree of T-cell requirement for the memory generation is very low, and (3) priming with too much strong stimulation in the absence of functional T cells leads to the suppression or abortion of previously generated immunological memory. [ABSTRACT FROM AUTHOR]

Nude and normal CBA mice have been used in adoptive transfer experiments to analyse the development of immunological memory. The development of B-cell memory to xenogeneic erythrocyte antigens is to a very large degree dependent on the presence of T cells, wit h IgG memory being somewhat more dependent than IgM memory. In this system, the expression of B memory, that is the transformation of memory cells to antibody-secreting cells under the inductive influence of antigen, is largely dependent on the presence of T cells. Primed (educated) T cells can have an antigen-specific potentiating effect on unprimed B cells in the presence of antigen. [ABSTRACT FROM AUTHOR]

Thymectomized NIH and C57BL mice were more susceptible to Piasmodiurn chabaudi than controls, indicating a role for T cells in acquired immunity to the parasite. Enriched populations of T and B cells were prepared from the spleens of immune mice using nylonwool columns, and were adoptively transferred to syngeneic non-irradiated mice or mice irradiated with 600 or 800 tad. Some immunity could usually be transferred with immune T, B and glass-wool (g.w.) filtered spleen cell populations. In the heavily irradiated mice g.w. filtered immune spleen cells gave the best protection and the immune T cells the least. Preliminary attempts to show synergistic activity between immune T and B cells in irradiated mice were not successful. [ABSTRACT FROM AUTHOR]

The mouse T-cell tumours El -4 and WEHI-22 produce an immunoglobulin (TCT Ig) which suppresses the antibody response to T- dependent antigens in vitro while having no effect on responses to T-independent antigens. TCT Ig also augments IgG responses to both kinds of antigen. TCT Ig appears to be a new class of mouse Ig because its effects on in vitro antibody responses can be absorbed by antisera to mouse Kappa chains but not with antisera to any of the known classes of mouse Ig. Furthermore, TCT Ig activity cannot be duplicated by free light chains, Fab2 fragments, several mouse serum Ig preparations or Ig made from B cells. TCT Ig affects only T-cell function in antibody responses. It has no effect on the ability of the different subclasses of T cells to respond to mitogens or to alloantigens. Furthermore, it does not block T-T-cell co-operation suggesting that the molecular basis for T-T co-operation differs from that of T-B co-operations. [ABSTRACT FROM AUTHOR]

Delayed hypersensitivity to staphylococcal antigens was shown m mice repeatedly infected with Staphylococcus aureus. It was characterized by footpad swelling at 48 hours with a mononuclear cell infiltrate and could be transferred to non-infected recipients by T lymphocytes from infected animals, but not by serum. Recipients of immune T cells produced very severe necrotic lesions when challenged with staphylococci. This was in contrast to the protection against necrosis in recipients afforded by serum from infected donors. When both serum and cells were transferred into the same mouse thc humoral effects overshadowed or perhaps inhibited those mediated by cells with resultant protection against staphylococcal dermonecrosis. [ABSTRACT FROM AUTHOR]

The aim of the experiments was to find a T cell-mediated cytotoxic reaction where genetically determined low responsiveness is under the control of recessive genes. The T cell-mediated immune response to DBA/2 mastocytoma cells P 815-X2 in different inbred strains, F1 hybrids and congenic resistant strains of mice was determined using the 51Crk-release method. Two types of low responsiveness were found. The first already well documented type is characterized by dominance of low responsiveness in genetical analysis. It is due to tolerance because of the identity of the H-2 linked specificities of the recipient and of DBA/2 (H-2d) mice from which the turnout is derived. The second and new type of low responsiveness in T cell-mediated immunity was found in DBA/1 mice. In this strain low responsiveness is inherited as a recessive trait. The cytotoxic response of DBA/1J mice against the C57B1/6 lymphoma EL 4 is normal. Thus, their low responsiveness is restricted to a limited number of membrane determinants. [ABSTRACT FROM AUTHOR]

The mouse Nrampl (Bcg) gene on chromosome 1 exerts pleiotropk effects on macrophage function. The gene is known to affect presentation of mycobacteria, and other antigens in vitro, so that macrophages carrying the resistant Bcg allele better support the proliferation of antigen-specific T cells compared with macrophages of the sensitive phenotype. To determine whether the Bcg allele could affect in vivo the antibody response to antigens not related to mycobacterial infections, we tested the primary and secondary responses to sheep red blood cells (SRBC) and glycosylated bovine insulin (G-insulin) in two pairs of Bcg congenic strains: BALB/c (Bcgs) versus BALB/c.CD2 (Bcgr), and B10.A (Bcgs) versus B10Ar (Bcgr), and in C57BL/10ScSn (B10; Bcgs) and A/J (Bcgr) mict. Furthermore, the antigen-specific proliferative responses of T cells primed in vivo by protein antigens were also tested in Bcg congenic mice. We found no significant difference in vim antibody response either to SRBC or G-insulin between the Bcgr and Bcgs strains. The magnitude of in vitro antigen-specific proliferation of lymph node cells sensitized in vivo by hen egg lysozyme (HEL) or chicken ovalbumin (OVA) was also similar in Bcgs and Bcgr congenic mice. However, we have documented a higher antigen-presenting capacity of Bcgr macrophages in vitro antigen-specific proliferation to OVA. Since the macrophages are the only cells in which the Nrampl gene is expressed, we suggest that the activity of other types of antigen-presenting cells masks the effect of the Bcgr allele on antigen-presentation in vivo. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is a facultative intracellular pathogen that replicates inside mononuclear phagocytes and induces specific cellular immunity. Listeriosis encompasses many clinical syndromes and meningitis is the most frequent clinical manifestation. Human α/β and γ/δ T cells have been shown to respond to L. monocytogenes antigens and to play an important role in resistance against listerial infection. We investigated the nature of listerial ligands and the influence of the major virulence factor, listeriolysin (hly), on the stimulation of human γ/δ T cells from healthy individuals. We found that a listerial somatic protein ligand, which is sensitive to proteinase treatment, stimulated γ/δ T cells in vitro; the majority of Listeria-responsive γ/δ T cells expressed Vγ9Vδ2 T-cell receptor chains and human leucocyte antigen-DR molecules; γ/δ T-cell responses to hly+ and hly- Listeria strains were comparable; L. monocytogenes strains of different virulence stimulated γ/δ T cells equally. Thus, protein components of L. monocytogenes unrelated to virulence activate human γ/δ T cells in vitro. [ABSTRACT FROM AUTHOR]

Polarized expression of T-helper type-1 (Th1)- or Th2-like patterns of cytokine production frequently correlates with disease outcome. Previously, we have described the long-lived reciprocal regulation of ovalbumin (OVA)-specific IgE (> 95% inhibition) and IgG2a (300–800-fold increased) production following administration of high MW OVA polymers (OVA-POL), in both de novo and ongoing OVA (alum)-induced responses. Here, limiting dilution analysis (LDA) was used to compare precursor frequencies of CD4 T cells producing interferon-γ (IFN-γ), interleukin-4 (IL-4) or IL-10 following OVA versus OVA-POL exposure in vivo. Adjuvants were not used, so as to circumvent their impact on measurement of precursor frequencies. We found that the two forms of antigen elicited T-cell activation of comparable intensity, as indicated by equivalent precursor frequencies of clonogenic antigen-specific CD4 T cells. However, they elicited qualitatively different cytokine responses. OVA-POL treatment led to 10-fold higher (mean of six independent LDA experiments) frequencies of IFN-γ-producing cells, and a mean fivefold lower frequency of IL-10-producing cells, than was observed following in vivo administration of unmodified OVA. Thus, the high MW polymerized form of antigen acted to steer commitment of naive (for this antigen) CD4 T-cell activation from a situation in which IL-10 producers outnumbered IFN-γ-producing cells by a factor of 4:1 (found in mice administered OVA), to one where IFN-γ producers dominated by a factor of 11:1 (in mice given OVA-POL), i.e. a qualitative shift in the nature of the OVA-specific response induced from Th2-1ike to Th1-like. In vivo co-administration of anti-IFN-γ monoclonal antibody (mAb) abolished the capacity of OVA-POL to preferentially elicit Th1-like dominance. Interestingly. although the ratios of IFN-γ:IL-4 and IFN-γ:IL-10 OVA-specific precursor frequencies were strongly increased following OVA-POL exposure (mean 18- and 47-fold higher), the frequency of IL-4-producing CD4 T cells did not differ significantly. The data suggest that this modified antigen promotes in vivo commitment of naive T cells towards a Th1-like response, with consequent inhibition of IgE and enhancement of IgG2a responses, not through direct effects on IL-4 production, but via decreased frequencies of IL-10 and increased frequencies of IFN-γ-producing OVA-specific CD4 cells. Collectively, the data (1) demonstrate the ability to manipulate commitment of antigen-driven CD4 T-cell populations in naive mice to specific patterns of cytokine gene expression, and (2) provide in vivo evidence of the regulatory role played by IFN-γ in limiting induction and/or expansion of IL-4- and IL-10-producing CD4 cells to protein allergens. [ABSTRACT FROM AUTHOR]

In this study, we examined the ability of varying populations of donor cells from B6 mice to induce hyporesponsiveness in T lymphocytes from C3H mice in vitro and in vivo. Small, resting B lymphocytes were inefficient stimulators of T-lymphocyte proliferation compared to splenic mononuclear cells (SMNC) and lipopolysaccharide (LPS)-induced B-cell blasts in vitro (P < 0.05). Pretreatment of SMNC with anti-B7-1 or anti-intracellular adhesion molecule-1 (ICAM-1) monoclonal antibodies (mAb) similarly resulted in inefficient stimulation of T-cell proliferation in vitro (P < 0.05). However, in vivo, only intrahepatic, but not intravenous, injection of donor cells into C3H mice resulted in decreased T-lymphocyte proliferation in response to restimulation by alloantigen. This effect was most pronounced following intrahepatic injection of resting B lymphocytes or SMNC pretreated with anti-ICAM-1 mAb compared to uninjected or intravenously injected mice (P < 0.05). The hyporesponsiveness was associated with an increased production of interleukin-4 (IL-4) by the responder T lymphocytes and correlated with enhanced skin allograft survival. These data demonstrate that intrahepatic injection of donor-derived cells induces T-lymphocyte hyporesponsiveness. The mechanism appears to be modulated by an ICAM-1-mediated signal resulting in expansion of an IL-4-producing T-lymphocyte population. [ABSTRACT FROM AUTHOR]

In this study the involvement of peripheral γδ T cells, prepared by flow cytometry, in the immune response of cattle to primary infection with Trypanosoma congolense was assessed. Negligible in vitro proliferative responses were observed in γδ T cells isolated from trypanosusceptible Boran (Bos indicus) cattle at all stages examined post-infection when stimulated in vitro with parasite antigens. In contrast, both CD8+ T cells and γδ T cells from trypanotolerant N'Dama (Bos taurus) cattle proliferated markedly when stimulated in vitro with a complex of invariant trypanosome antigens with MW between 100 000 and 140 000 (100 000 MW complex). Neither species of cattle exhibited significant T-cell recognition of trypanosome variable surface glycoprotein (VSG). To study further the functional and phenotypic characteristics of the γδ T-cell response, four T-cell lines were established from infected N'Dama cattle. These cell lines were comprised of up to 96% γδ (WC1+) T cells, the remainder being CD8+ T cells. Two of these γδ T-cell lines exhibited 100 000 MW complex antigen specificity which was not major histocompatibility complex (MHC) restricted in one line. [ABSTRACT FROM AUTHOR]

BoCD4+T-cell clones specific for a peptide derived from foot-and-month disease virus envelope protein, VP1 (FMDV15) were generated from two responder cattle. One animal was a high and the other was an intermediate responder in terms of both T-cell and antibody responses. However both animals had identical major histocompatibility complex (MHC) class II DR-like types (DRBF3,6) according to a one-dimensional isoelectric focusing method which distinguishes DR-like alleles. In contrast, mixed lymphocyte reaction (MLR) responses indicated that they shared only one haplotype (DRBF3) and anti-DRBF6 alloclones also differentiated between the animals. This suggested that the animals differed at a non-DR-like locus. Restriction patterns of FMDV-specific clones derived from these animals indicated that FMDV15 was presented by the non-DR-like class II molecules associated with DRBF6. Only one clone, derived from the high responder animal, was restricted to DRBF3. Thus products from the non-DR-like locus (probably DQ-like) are functionally important for presentation of FMDV peptides. Furthermore the allelic differences detected by the alloclones are also critical for peptide binding. The majority of clones from the high responder animal recognized an immunodominant region containing a Rothbard epitope whereas none of the clones from the intermediate responder did so. This suggests that the region recognized by T cells, which is dependent upon MHC type, influences the B-cell response and thus the degree of protection obtained. This has major implications for rational vaccine design involving T- and B-cell epitopes. [ABSTRACT FROM AUTHOR]

During primary tsetse-transmitted challenge of Boran (Bos indicus) cattle with Trypanosoma congolense ILNat 3.1, a transient parasite antigen-specific T-cell proliferative response was observed in peripheral blood mononuclear cells and splenic mononuclear cells stimulated in vitro. A response was also observed with cells of N'Dama (Bos taurus) cattle, but in this case higher stimulation indices were observed and the response was maintained until the termination of the experiment at 40 days post-infection (p.i.). The highest parasite antigen-specific proliferative responses were observed at 20 days post-infection. At this time N'Dama cattle not only responded to the antigens derived from the infecting clone (ILNat 3.1), but also to antigens from a clone of a different serodeme (ILNaR 2), whereas Boran cattle only recognized antigens from the infecting clone of parasites. To determine the molecular mass of the antigenic trypanosome proteins, whole trypanosome lysates made from T. congolense ILNat 3.1 were fractionated by SDS-PAGE and transferred onto nitrocellulose membranes. The major protein bands were isolated and used directly in T-cell proliferation assays, In this instance, no differences in the antigen recognition profiles of Boran and N'Dama cattle were observed. The variable surface glycoprotein did not induce T-cell proliferation in infected cattle despite the presence of serum antibodies to this variable antigenic type. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) have a potent antigen-presenting capacity for recruiting resting T cells into immune responses. They also promote expansion of already activated memory T cells. By contrast, macrophages (Mø) are only effective in stimulating memory responses.¹, ² Infection and depletion of DC occur in human immunodeficiency virus (HIV)-infected individuals and recruitment of T cells into primary responses is blocked.³ Here comparisons between DC and Mø in stimulating secondary T-cell responses in HIV infection were made. Adherent Mø, and DC isolated by a new method, were separated from peripheral blood of patients in different stages of HIV infection and from uninfected controls and added to allogeneic lymphocytes in mixed leucocyte reactions (MLR). Some were pulsed with influenza virus or tetanus toxoid and used to stimulate autologous T cells. Responses were measured from uptake of [³H]thymidine in 20 μ1 hanging drop cultures. DC, but not Mø, from normal individuals stimulated MLR but both populations stimulated secondary responses to recall antigens. DC from all HIV seropositive individuals caused little or no stimulation of any lymphocyte responses. However, Mø from HIV seropositive asymptomatic individuals and those with persistent generalized lymphadenopathy stimulated responses to recall antigens. There was no stimulation using cells from acquired immune deficiency syndrome (AIDS) patients. Blocked DC but not Mø function may underlie progressive immunological non-responsiveness in HIV infection. Without recruitment of resting T cells, loss of memory T cells4–6 may be cumulative; failure of secondary activation (e.g. by Mø) would lead to lost T-cell activity. Identification and circumvention of the defect in DC could offer new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Infection in mice with an attenuated strain of Salmonella abortusovis (SAO), a specific pathogen for sheep, was used as a convenient model to understand further the induced immunity against SAO. The hypovirulent Rv6 strain, subcutaneously inoculated in salmonella-susceptible BALB/cby (Ity') mice, colonized the spleen and the liver in less than 6 days post-infection (PI) to be cleared after Day 28 PI. Simultaneously, an increase in spleen cell numbers, splenomegaly and hepatic granulomatous lesions developed to a maximum level on Day 9 PI. In spleen of uninfected mice, the number of Thy-1.2+ cells represents twice the number of surface immunoglobulin-positive cells (sIg+). Cytofluorometric analysis of the spleen lymphoid cell subsets showed a significant increase (10 times, P<0.05)in the number of sIg+ cells from Day 6 to Day 28 PI compared to control values. The number of Thy-1.2+ cells also significantly increased, to a lesser degree than the sIg+ cells, on Day 2 and on Day 16 PI (twice control values, P&lt0.05), but decreased on Day 6 PI compared to Day 2 PI. The highest L3T4+:Lyt-2+ ratio was observed on Day 2 PI and the lowest on Day 9 PI. On Day 28 PI, the number of sIg+ cells was still greater than the number of Thy-l.2+ cells. The granulomatous lesions were observed in the liver as early as Day 2 PI and their frequency was maximal on Day 9 PI. Immunohistochemical analysis of the granulomatous lesions showed that macrophages (F4/80+, Macl+) were the basic cells and that L3T4+ cells were the predominant T cells. In well-developed granulomas observed on Day 9 PI, macrophages were in the centre whereas L3T4+ T cells were preferentially located at the periphery. T cells expressing Lyt-2 antigen were rarely detected. Variations in the proportion of lymphoid cells in the spleen and in hepatic granulomatous lesions suggest different and complementary effector mechanisms in induced immunity against SAO. [ABSTRACT FROM AUTHOR]

The H-Y-expressing murine tumour, ET-5, specifically immunizes B6 female mice that have rejected it against H-Y-positive male skin grafts, yet fails to prime their spleen cells for the generation of H-Yspecific cytotoxic T lymphocytes (CTL). ET-5 also fails to prime relevant congenic hosts to generate CTL specific for H-3 or H-25 minor H antigens, or major histocompatibility complex (MHC) class I antigens, all of which are expressed in immunogenic form by ET-5. Nonetheless, C3H.SW mice, which are MHC-compatible with B6 mice in which ET-5 originated, but differ from B6 at many minor H loci, can be primed to generate CTL directed against one or more unidentified minor H antigens. These CTL are conventional MHC-restricted, CD8+ T cells, and require priming in vivo for their generation. Significantly, C3H.SW females can be primed by ET-5 to generate B6-specific CTL, but not H-Y-specific CTL. Thus CTL priming is selective in the sense that ET-5 primes CTL specific for some of the antigens it expresses but not others. The basis for this selectivity is not known but, in the case of H-Y antigen, it appears not to result from an inability of ET-5 to express either H-2Dbencoded antigens, the restriction element for H-Y-specific CTL in B6 females, or H-Y itself in vivo. [ABSTRACT FROM AUTHOR]

The results of this study show that acquired protective immunity to Listeria monocytogenes, measured as the capacity of splenic T cells to passively transfer acquired resistance to normal syngeneic recipients, was mediated by a population of cyclophosphamide-sensitive CD4- CD8+ T cells. The results further show, in contrast, that memory immunity to listeriosis, which was defined as resistance transferred by T cells harvested from infected animals that had received ampicillin chemotherapy, was shown to be mediated by cyclophosphamide-resistant CD4+ CD8- T cells. [ABSTRACT FROM AUTHOR]