Immune T cells sorted by flow cytometry confer protection against infection with Treponema pallidum subsp. pertenue in hamsters.

The role of cell-mediated immunity against infection with Treponema pallidum subsp. pertenue in humans or experimental animals is unclear. Hamsters injected subcutaneously in the hind paws with 4 x 10(6) unfractionated lymph node cells or enriched lymph node T cells (immunoglobulin negative, Ia negative) from T. pallidum subsp. pertenue-immune hamsters were resistant to challenge with T. pallidum subsp. pertenue. The popliteal lymph nodes of hamsters that received immune cells weighed less and had significantly fewer treponemes than did lymph nodes from hamsters infused with cells from nonimmune donors. Furthermore, recipients of immune T cells failed to develop antitreponemal antibodies 21 days after challenge. Enriched T cells were obtained by flow cytometric separation by using monoclonal anti-Ia antibody 14-4-4s, which identified hamster B cells. Flow cytometric analysis by two-color immunofluorescent staining with anti-hamster-immunoglobulin and monoclonal anti-Ia antibody 14-4-4s confirmed that monoclonal anti-Ia antibody 14-4-4s recognized B cells. In addition, lymph node cells obtained after treatment with anti-Ia monoclonal antibody 14-4-4s and complement were 97% T cells, as determined by monoclonal antibody 20, a hamster T-cell marker. These results demonstrated that highly enriched T cells (immunoglobulin negative, Ia negative) from T. pallidum subsp. pertenue-immune hamsters conferred partial protection on hamsters against infection with T. pallidum subsp. pertenue.     

CD8+ alphabeta T cells can mediate late airway responses and airway eosinophilia in rats

BACKGROUND: The function of CD8+ T-cell subsets in mediating late allergic responses is incompletely understood. OBJECTIVE: We sought to test the hypothesis that CD8+ alphabeta T cells are proinflammatory in the airways in vivo by using a well-characterized animal model and the technique of adoptive transfer. METHODS: Brown Norway rats were administered CD8 + alphabeta T cells (10 6 ) intraperitoneally purified from lymph node cells of either naive or ovalbumin (OVA)-sensitized rats and were challenged with aerosolized OVA 2 days later. Control rats were sensitized to 100 mug of OVA in Al(OH) 3 subcutaneously or sham sensitized to saline and were OVA challenged 2 weeks later. RESULTS: The OVA-sensitized and OVA-challenged group and the recipients of OVA-primed CD8+ alphabeta T cells had significant late airway responses calculated from lung resistance measured for an 8-hour period after challenge compared with the naive CD8 + alphabeta T cell-transferred group and the sham-sensitized control group. The number of eosinophils in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with numbers in the naive CD8+ alphabeta T-cell recipients and the sham-sensitized control group. IL-4 and IL-5 cytokine mRNA expression in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with that in the sham-sensitized group. CONCLUSION: We conclude that antigen-primed CD8 + alphabeta T cells might have a proinflammatory role in allergen-driven airway responses in the rat.     

Mediation of immunity to Eimeria vermiformis in mice by L3T4+ T cells.

Immunity to infection with Eimeria vermiformis was transferred in NIH mice by both the nylon wool-adherent (B-cell-enriched) and nonadherent (T-cell-enriched) fractions of lymphocytes (spleen and mesenteric lymph node) taken from infected donors. Transfer was more variable with the adherent fraction, and when contaminating T cells were removed by treatment with anti-Thy1 monoclonal antibody (MAb) and complement, this fraction lost all protective activity. The protective effect of T-cell-enriched populations of mesenteric lymphocytes was abrogated by treatment with anti-L3T4 MAb and complement in vitro before transfer or by opsonization with this MAb in vitro before intravenous inoculation into recipients. Similar treatments of cells with anti-Lyt2 MAb did not have this effect, confirming that Thy1+ L3T4+ cells mediate the adoptive transfer of immunity to E. vermiformis. Thy1+ L3T4+ cells were also shown to limit the replication of E. vermiformis in primary infections: mice depleted of this subset (by thymectomy followed by intravenous injection of anti-L3T4 MAb) passed greater numbers of oocysts over a longer period of time than did mice similarly depleted of Lyt2+ cells.     

T-cell subsets in delayed-type hypersensitivity, protection, and granuloma formation in primary and secondary Listeria infection in mice: superior role of Lyt-2+ cells in acquired immunity.

Immunity to Listeria monocytogenes was studied in mice treated with rat monoclonal antibodies (MAbs) specific for the Thy-1.2, L3T4, and Lyt-2 T-cell markers. Three characteristic T-cell-mediated phenomena were investigated. Delayed-type hypersensitivity (DTH) to listerial antigen was totally abolished in mice treated with anti-Thy-1.2 or anti-L3T4 MAbs, whereas anti-Lyt-2 MAb treatment had no effect, regardless of whether the MAb was given during the induction or the expression of DTH. On the other hand, the elimination of bacteria from the spleens of infected animals was inhibited only by the application of either anti-Thy-1.2 MAb or anti-Lyt-2 MAb. This could be shown most impressively during the secondary infection of immune mice with a normally lethal dose of listeriae. In this situation, treatment with anti-Lyt-2 MAb sufficed to completely abolish immunologic memory, whereas anti-L3T4 MAb had only a marginal effect on antibacterial protection. However, the accelerated development of mononuclear cell foci in the livers of immune mice was inhibited by the application of both anti-L3T4 MAb and anti-Lyt-2 MAb. It is concluded that in murine listeriosis, DTH and acquired immunity to reinfection are dissociable phenomena. Although DTH is a function of L3T4+ T lymphocytes, Lyt-2+ T cells are necessary and sufficient for the expression of acquired resistance to L. monocytogenes. The roles of the different T-cell subsets in granuloma formation warrant further investigation.     

CD4+ T cells migrate from airway to bone marrow after antigen inhalation in rats

BACKGROUND: IL-5-producing T lymphocytes increase in rat bone marrow after inhalational challenge with allergen. OBJECTIVE: To test the hypothesis that T cells migrate from the airways to the marrow, we examined the trafficking of T cells in Brown Norway rats after sensitization and challenge with ovalbumin. METHODS: Purified CD4+ T cells, harvested from cervical lymph nodes of naive and ovalbumin-sensitized donors, were labeled with carboxy fluorescein diacetate succinimidyl ester; 20 x 10(6) cells were placed in the trachea of naive or sensitized recipients under anesthesia, and 18 hours later, animals were challenged with inhaled ovalbumin. Cells were harvested 24 hours later from the bone marrow, bronchoalveolar lavage fluid, lungs, the lung blood pool of cells, lung draining lymph nodes, peripheral blood, and spleen. RESULTS: The number of carboxy fluorescein diacetate succinimidyl ester-positive cells, measured by fluorescence-activated cell sorter, in the bone marrow of ovalbumin sensitized, primed T-cell recipients was higher than either the sham-sensitized, primed T-cell recipients or sham-sensitized, naive T-cell recipients (P < .05). The number of eosinophils in both bone marrow and bronchoalveolar lavage fluid was increased in ovalbumin-sensitized, primed T-cell recipients. The expression of the T-cell chemoattractants eotaxin and IL-16, evaluated by immunohistochemistry, was higher in the bone marrow of ovalbumin-sensitized, primed T-cell recipients. CONCLUSIONS: CD4+ T cells travel from airway to bone marrow after antigen inhalation. The homing of the CD4+ T cells might be facilitated by eotaxin and IL-16 expression in the bone marrow and might contribute to the stimulation of eosinophilopoiesis after airway allergen exposure.     

Effective protection against Listeria monocytogenes and delayed-type hypersensitivity to listerial antigens depend on cooperation between specific L3T4+ and Lyt 2+ T cells.

Selected L3T4- and Lyt 2- T-cell subpopulations from Listeria monocytogenes-infected mice were transferred into syngenic recipients, and their capacity to adoptively mediate protection against L. monocytogenes and delayed-type hypersensitivity to listerial antigens was determined. Both functions were markedly reduced by pretreatment of cells with either anti-L3T4 or anti-Lyt 2.2 antibodies plus complement, but they could be restored by admixture of the two selected T-cell subsets. Thus, after systemic cell transfer effective protection against L. monocytogenes and delayed-type hypersensitivity to listerial antigens depend on cooperation between specific L3T4+ and Lyt 2+ T cells.     

Proliferation of human CD4+45R+ and CD4+45R- T helper cells is promoted by both IL-2 and IL-4 while interferon-gamma production is restricted to IL-2 activated CD4+45R- T cells

Recombinant IL-2 (rIL-2) and IL-4 (rIL-4) promote proliferation of human CD4+ T cells activated in the presence of PHA, TPA or OKT-3 monoclonal antibody (MAb), whereas the production of interferon-gamma (IFN) can be induced only by rIL-2. rIL-4 induced strong proliferative responses both in accessory cell independent assays and in the presence of autologous monocytes, but has failed to induce IFN production in any of these systems. The ability of rIL-2 to induce IFN production was strongly enhanced by the addition of monocytes, although a similar proliferative response was recorded in the absence or presence of monocytes. The MAb anti-Tac inhibited the proliferative response and the production of IFN by CD4+ T cells activated in the presence of rIL-2, whereas the proliferative response to rIL-4 was unaffected. CD4+45R+ and CD4+45R- T helper cell subsets proliferated in response to both IL-2 and IL-4. A kinetic analysis demonstrated that the production of IFN throughout a five day activation period was restricted to stimulation of CD4+45R- T cells with rIL-2. This report clearly demonstrates a dissociation of IFN production and T cell proliferation in man. While proliferation can be induced by both IL-2 and IL-4 in both the helper T cell subsets studied, IFN production was induced only in the CD4+45R- subsets and only in response to IL-2.     

Passive transfer of resistance to frambesial infection in hamsters.

The immune mechanism by which hamsters acquire resistance to infection with Treponema pertenue, the causative agent of frambesia, or yaws, has not been elucidated. Serum or cells (spleen or lymph node) obtained from hamsters resistant to frambesial infection were transferred to normal syngenic recipients, who are subsequently infected with T. pertenue. The following parameters were used to measure the ability of immune serum of cells to confer resistance on recipient hamsters to frambesial infection: inhibition of the development of cutaneous lesions, decreased weight, and number of treponemes in the inguinal lymph nodes. This investigation demonstrated that immune serum conferred protection on recipient hamsters infected with T. pertenue. Discontinuation of the administration of immune serum (18 days after frambesial infection) did not result in the development of cutaneous lesions. Since the inguinal lymph nodes contained a sizeable number of treponemes (2.6 X 10(5)), immune serum failed to prevent frambesial infection. Recipients of immune spleen or lymph node cells initially developed frambesial lesions 9 days after infection. The frambesial lesions began to resolve 12 to 14 days after infection and by day 21 had completely regressed. These results illustrated that humoral factors and cells are involved in resistance of the hamster to frambesial infection.     

Lymphocyte function in experimental endemic syphilis of Syrian hamsters.

We have studied the changes in the lymph nodes, spleen and thymus that occur in inbred LSH Syrian hamsters infected with Treponema pallidum Bosnia A, the causative agent of endemic syphilis, as well as the B-cell responses of these infected animals to helper T-cell independent and dependent antigens. The lymph nodes increased significantly in weight up to 6 weeks after infection, and contained viable treponemes. No significant changes in the spleen weight were observed, and no viable treponemes could be recovered from the spleen. However, the size of the thymus decreased steadily during the course of the disease. The relative number of Ig+ cells (B cells) increased in the spleen and regional lymph nodes, whereas the relative number of T cells decreased during the course of infection. In both the spleen and lymph nodes, the relative number of macrophages increased initially and decreased thereafter in the form of a bell-shaped curve showing a peak at 4-6 weeks of infection. The ability of splenic lymphocytes from infected hamsters to mount a primary PFC response to pneumococcal polysaccharide type III (SIII), a helper T-cell independent antigen, was elevated throughout the course of infection. However, the splenic PFC response to sheep erythrocytes (SRBC), a helper T-cell dependent antigen, was increased only during the first 4 weeks of infection and progressively decreased thereafter. The PFC responses of infected lymph node lymphocytes to both SIII and SRBC were increased during the first 4 weeks and decreased thereafter. These data suggested that atrophy of the thymus seen in syphilitic infection is accompanied by the complex losses of subsets of T cells and altered B-cell functions. An early loss of suppressor T cells in both the lymph nodes and spleen occurs concomitantly with a loss of T helper cells and heterologous (treponema-unrelated) B-cell functions in the lymph nodes. Helper T cells are lost from the spleen only in the later stages of infection, whereas splenic B-cell functions remain intact throughout the course of the disease. These findings were further tested by in vitro methods where splenic and lymph node lymphocytes from infected hamsters were examined for their ability to respond to Con A in terms of the induction of antigen non-specific suppressor T cells. The mixing of Con A stimulated splenic or lymph node lymphocytes from infected hamsters was unable to inhibit the primary antibody responses of SRBC as compared to the normal control.(ABSTRACT TRUNCATED AT 400 WORDS)     

Helper CD4+ T cells for IgE response to a dietary antigen develop in the liver

BACKGROUND: Although T-cell responses to food antigens are normally inhibited either by deletion, active suppression, or both of antigen-specific T cells, T helper cells for IgE response to a food antigen still develop by unknown mechanisms in a genetically susceptible host. OBJECTIVE: We determined the site at which those IgE helper T cells develop. METHODS: We administered ovalbumin (OVA) orally to DO11.10 mice and studied CD4+ T cells in Peyer's patches, the spleen, and the liver. Helper activity for IgE response was assessed by adoptively transferring those CD4+ T cells to naive BALB/c mice, followed by systemic immunization with OVA. RESULTS: OVA-specific CD4+ T cells were deleted by cell death in the liver and Peyer's patches of DO11.10 mice fed OVA. OVA-specific CD4+ T cells that survived apoptosis in the liver expressed Fas ligand and secreted IL-4, IL-10, and transforming growth factor beta(1). CD4+ T cells producing IFN-gamma were deleted in the liver by repeated feeding of OVA. On transfer of CD4+ T cells to naive mice and systemic immunization with OVA, a marked increase in OVA-specific IgE response developed only in the mice that received hepatic CD4+ T cells from OVA-fed mice, the effect of which was not observed in the recipients of hepatic CD4+ T cells deficient in IL-4. In addition, significant suppression of delayed-type hypersensitivity and IgG(1)/IgG(2a) responses to OVA was observed in the recipients of hepatic CD4+ T cells, and this suppression required Fas/Fas ligand interaction. CONCLUSION: Together, these results suggested that a food antigen might negatively select helper T cells for IgE response to the antigen by preferential deletion of T(H)1 cells in the liver.     

Acquired resistance of hamsters to challenge with homologous and heterologous virulent treponemes.

Hamsters infected with Treponema pallidum Nichols (venereal syphilis), T. pallidum Bosnia A (endemic syphilis), or T. pertenue (frambesia, or yaws) developed substantial resistance to homologous reinfection. Hamsters infected for 10 weeks developed no lesions, and their lymph nodes contained fewer treponemes after reinfection with the same strain. The degree of cross-resistance among the treponemes correlated well with pathological changes occurring in infected hamsters and with the persistence of treponemal antigen during primary infection. Only hamsters infected with T. pallidum Bosnia A developed substantial resistance to heterologous reinfection. These animals also had extensive chronic skin lesions and lymph nodes containing measurable numbers of treponemes. Frambesial hamsters had less extensive lesions and were resistant to T. pallidum Nichols and, to a lesser extent, to T. pallidum Bosnia A. Hamsters infected with T. pallidum Nichols developed no cutaneous lesions and were resistant only to reinfection with T. pertenue. Confirmation of these results was obtained in normal hamsters infused with syphilitic (Nichols or Bosnia A) or frambesial immune cells and challenged with homologous or heterologous treponemes.     

Instruction of naive CD4+ T-cell fate to T-bet expression and T helper 1 development: roles of T-cell receptor-mediated signals

Using T-cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4(+) T cells induces transient T-bet expression, interleukin (IL)-12 receptor beta2 up-regulation, and GATA-3 down-regulation, which leads to T helper (Th)1 differentiation even when the cells are stimulated with peptide-loaded I-A(b)-transfected Chinese hamster ovary cells in the absence of interferon-gamma (IFN-gamma) and IL-12. Sustained IFN-gamma and IL-12 stimulation augments naive T-cell differentiation into Th1 cells. Intriguingly, a significant Th1 response is observed even when T-bet(-/-) naive CD4(+) T cells are stimulated through TCR in the absence of IFN-gamma or IL-12. Stimulation of naive CD4(+) T cells in the absence of IFN-gamma or IL-12 with altered peptide ligand, whose avidity to the TCR is lower than that of original peptide, fails to up-regulate transient T-bet expression, sustains GATA-3 expression, and induces differentiation into Th2 cells. These results support the notion that direct interaction between TCR and peptide-loaded antigen-presenting cells, even in the absence of T-bet expression and costimulatory signals, primarily determine the fate of naive CD4(+) T cells to Th1 cells.     

Preferential expression of IL-2 receptor subunits on memory populations within CD4+ and CD8+ T cells.

Using anti-Tac and anti-Mik-beta 1 monoclonal antibodies to alpha and beta subunits of the interleukin-2 receptor (IL-2R), respectively, a marked difference in expression of IL-2R subunits on blood CD4+ and CD8+ T cells was demonstrated between adults and newborns. In the adult blood, reciprocal expression of IL-2R alpha and IL-2R beta was observed in CD4+ and CD8+ T cells. Some CD4+ T cells expressing IL-2R alpha were often detected, but IL-2R beta + CD4+ cells were very few. On the other hand, CD8+ T cells expressed significant IL-2R beta but little IL-2R alpha. In marked contrast to adult individuals, both CD4+ and CD8+ T cells from the newborns, which seemed to consist mainly of naive populations, showed only negligible expression of IL-2R subunits. It was found that IL-2R subunits appeared to be preferentially expressed on CD4+ and CD8+ T cells with memory phenotypes in the adult blood. Isolated memory (CD45RO+) CD4+ and CD8+ T cells, unlike naive (CD45RO-) ones, were able to proliferate in response to exogenous IL-2 as well as the recall antigen. The present results suggest that IL-2R subunits expressed on circulating T-cell subsets may play an important role in memory T-cell function.     

LSH hamster model of syphilitic infection.

The inbred LSH/Se LAK strain of hamster can be infected with Treponema pallidum Bosnia A, the causative agent of endemic syphilis. When infected, this strain consistently produced extensive chronic skin lesions that persisted for 6 to 9 months, even in the presence of peak antitreponemal antibody titers. The lymph nodes increased in weight and contained measurable numbers of treponemes. This infection also gave the hamster cross-immunity to T. pallidum Nichols and Treponema pertenue, the causative agents of venereal syphilis and frambesia, respectively. LSH hamsters are thus an excellent model to study the immune response mechanisms to syphilitic infection.     

Role of L3T4+ T cells in host defense against Histoplasma capsulatum.

Cell-mediated immunity is critical in host resistance against the pathogenic fungus Histoplasma capsulatum. To explore the role of L3T4+ T cells in protection of mice against H. capsulatum infection, we examined the effect of in vivo treatment with anti-L3T4 monoclonal antibody (MAb) GK1.5 on the course of murine disseminated histoplasmosis. Treatment with anti-L3T4 antibody caused a profound and selective depletion of L3T4+ T cells that was associated with a significant increase in the number of H. capsulatum CFU recovered from the spleens of mice infected for 1 week. In addition, none of the infected mice treated with MAb GK1.5 survived a sublethal challenge with H. capsulatum yeasts. Histopathological examination of spleens from mice infected for 1 week revealed the presence of granulomatous inflammation in mice depleted of L3T4+ T cells and in infected controls. However, silver stains demonstrated that spleens of infected mice given MAb GK1.5 contained a greater number of yeasts than did spleens from infected controls. MAb GK1.5 did not cause reactivation of infection when administered for 2 weeks beginning 4 weeks after inoculation of Histoplasma yeasts. MAb GK1.5 did not alter the functional properties of murine macrophages as measured by antigen presentation, production of interleukin-1 in response to lipopolysaccharide, and phagocytosis of H. capsulatum yeasts. These results suggest that the L3T4+ T-cell subset is an essential constituent of the cell-mediated immune defense against H. capsulatum infection.     

T-lymphocyte subsets in nude mice with Giardia muris infection

The aim of this study was to compare the relative percentages of T-lymphocyte subsets in athymic (nude) mice and immunocompetent BALB/c mice, with and without Giardia muris infection. Suspension of mononuclear leukocytes from blood, spleen, and Peyer's patches of uninfected mice were incubated with fluorescent monoclonal antibodies (MAbs) directed against mouse T-lymphocytes (anti-Thy-1.2 MAb), T helper/inducer lymphocytes (anti-L3T4 MAb), or T suppressor/cytotoxic lymphocytes (anti-Ly-2 MAb), and examined by fluorescence microscopy to quantify each of these cell populations. While the percentages of Thy-1.2+, L3T4+, and Ly-2+ lymphocytes are all reduced in nude mice, L3T4+ lymphocytes were found to be especially depleted, resulting in a reversed L3T4+/Ly-2+ ratio (less than 1) in all of the nude mouse tissues examined. BALB/c and nude mouse Peyer's patch T-cell subsets were quantified at various times during enteric Giardia muris infection. Unlike immunocompetent BALB/c mice, nude mice have an impaired ability to clear this infection. It was found that clearance of G. muris infection is associated with a Peyer's patch L3T4+/Ly-2+ ratio of greater than or equal to 2, and that this infection does not alter the percentages of Peyer's patch Thy-1.2+, L3T4+, or Ly-2+ lymphocytes in BALB/c mice or nude mice. The data obtained in the present work and in other studies suggest that the impaired capacity of nude mice to clear G. muris infection results from deficiency of L3T4+ lymphocytes.     

Putative role for interleukin-7 in the maintenance of the recirculating naive CD4+ T-cell pool

The capacity of the immune system to respond efficiently to new antigens depends upon a continuous source of naive CD4+ T cells. Such cells exit from the thymus and join the recirculated T-cell pool. Factors present at the sites of naive CD4+ T-cell circulation must be responsible for their survival, since upon removal from their host, naive CD4+ T cells die. However, such factors remain unknown. The presence of the cytokine interleukin-7 (IL-7) in secondary lymphoid organs and the continuous expression of its receptor on naive CD4+ T cells prompted us to examine the possibility that IL-7 might be a survival factor for naive CD4+ T cells. Using naive CD4+ T cells isolated from cord blood we show that IL-7, but not IL-2, can maintain naive CD4+ T-cell viability in vitro for at least 15 days. In addition, we find that IL-7 can induce modest proliferation of naive CD4+ T cells without affecting either their cell surface phenotype or their ability to respond to antigenic stimulation. We also find that after anti-CD3 stimulation, naive CD4+ T cells lose that ability to respond to IL-7. However, if cells are primed with IL-7 prior to antigenic stimulation, their proliferative responses are enhanced. Together, these data suggest a novel and important role for IL-7 in the maintenance and maturation of naive CD4+ T cells, ensuring that they can respond maximally when they first meet antigen in secondary lymphoid tissue.     

The dissociation of interleukin-2 production and antigen-specific helper activity by clonal analysis.

Influenza virus immune human T-lymphocyte clones maintained in continuous culture in TCGF were analysed for helper activity and interleukin-2 (IL-2) production. The clones that functioned as helper cells in the production of specific antibody failed to release detectable amounts of IL-2. Conversely, the T cells that produced IL-2 were unable to provide either specific or non-specific helper function. These findings indicated the IL-2 is not an essential component for helper activity. However, phenotypic analysis revealed that both the functional subsets of T-cell clones expressed the helper phenotype in that they were T4+, T3+ and T11+. Nevertheless analysis with other antibodies revealed differences in that the IL-2 releasing clone showed greater staining with the anti-T-cell subset antibodies 9.3 and Leu 8, confirming that there is phenotype as well as functional heterogeneity within the helper inducer T-cell population.     

T-cell receptor antagonist modifies cytokine secretion profile of naive CD4+ T cells and their differentiation into type-1 and type-2 helper T cells

A T-cell receptor (TCR) antagonist is an analog of a peptide ligand for TCR that inhibits T-cell responses to the original peptide. We investigated the effects of a TCR antagonist on cytokine secretion of naive CD4+ T cells and their differentiation into type-1 and type-2 helper T cells (Th1 and Th2) induced by stimulation with varying doses of an antigenic peptide. In the presence of a TCR antagonist peptide, proliferation of naive CD4+ T cells and antigen dose-dependent secretion of interferon-gamma, a typical Th1-type cytokine, by these cells was down-regulated. With respect to the secretion of interleukin-4 (IL-4), a typical Th2-type cytokine, the TCR antagonist raised the concentration of the antigenic peptide required to elicit maximal IL-4 production and, surprisingly, significantly increased the maximum level of IL-4 secretion. Similar effects induced by the TCR antagonist were observed on the Th1/Th2 differentiation of naive CD4+ T cells. These results clearly indicate that, for naive CD4+ T cells, a TCR antagonist has the potential to change the balance of Th1/Th2 cytokine secretion and even enhance Th2 responses.     

A new attempt to distinguish serologically the subspecies of Treponema pallidum causing syphilis and yaws.

In an effort to serologically differentiate syphilis from yaws, 69 monoclonal antibody species raised against Treponema pallidum subsp. pallidum were tested by immunoblotting for their reactivity with Treponema pallidum subsp. pertenue. All monoclonal antibodies reacted with antigens with the same molecular weight of both subspecies. Furthermore, no differences in reactivity between sera from yaws patients and from syphilis patients were found by Western blot (immunoblot) analysis of cell lysates of T. pallidum subsp. pallidum and T. pallidum subsp. pertenue. We tried to exploit the only known molecular difference between the subspecies. The subunits of the 190-kilodalton multimeric proteins TpF1 and TyF1 of T. pallidum subsp. pallidum and T. pallidum subsp. pertenue, respectively, have previously been shown to differ in one amino acid residue at position 40. In this study, no difference was found in immunoreactivity of TpF1 or TyF1 with either syphilis sera or yaws sera. Synthetic peptides based on the sequence of TpF1 and of TyF1 were used in an enzyme-linked immunosorbent assay with syphilis sera and yaws sera. Again, no difference in reactivity between the T. pallidum subsp. pallidum- and T. pallidum subsp. pertenue-derived peptides was observed.