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T cells from mice injected with picryl sulphonic acid (PSA) inhibit the expression of contact sensitivity to picryl chloride. Adult thymectomy (aTx) prevents the production of cells which inhibit the effector stage but cells from aTx mice are, however, still able to suppress the induction of contact sensitivity. These cells are antigen-specific T cells but unlike suppressor cells for the effector phase, they cannot be produced in cyclophosphamide (Cy)-treated mice. Similar properties have been reported for cells inhibiting the DNA synthesis in lymph nodes of mice painted with picryl chloride. It was also shown that cells from Cy-treated but non-thymectomized mice could not inhibit sensitivity when injected at the time of sensitization, i.e. suppressors of the effector phase, which are induced in Cy-treated mice cannot inhibit sensitivity when injected at the induction phase. These results show there are distinct mechanisms and probably distinct cells which inhibit the induction and expression of contact sensitivity. [ABSTRACT FROM AUTHOR]

T cells from mice painted with picryl chloride inhibit secondary IgG anti-TNP antibody responses of normal mice to the sensitizer. Like other suppressor T cells produced after painting which inhibit DNA synthesis and the generation of cytotoxic T cells, these cells could be produced in adult thymectomized mice but not by mice treated with high doses of cyclophosphamide (250 mg/kg). The cells had to be injected within 48 h of a primary painting to inhibit the response to challenge 2-3 weeks later. This associated with their ability to inhibit DNA synthesis in draining lymph nodes after a primary painting. Double transfer experiments using spleen and lymph node cells failed to show any further activation or induction of suppressor function after challenge with antigen. As judged by the ability of anti-O treated cells from suppressed mice to function as anti TNP primed B cells in adoptive responses to TNP-KLH no defect in B-cell memory was found. When, however, the ability of painting with picryl chloride to prime for challenge with TNP-KLH was used as a measure of B-cell function in situ it was found that the cells could inhibit responses. Responses to primary and secondary injections of TNP-KLH were not inhibited. [ABSTRACT FROM AUTHOR]

The anti-TNP antibody response of mice exposed to picryl chloride is a response where IgE antibody can be preferentially produced. Skin-painting with picryl chloride induces/gM, IgG and IgE antibody. After repeated painting the titre and persistence of the IgE but not tgG antibody is increased. Feeding picryl chloride does not induce antibody but it does produce unresponsiveness for IgG without affecting responsiveness for IgE. Injection of picryl sulphonic acid produces unresponsiveness for both classes. The unresponsiveness (induced by feeding or injection) is found for responses to picryl chloride but reponses to TNP-KLH are barely affected. Both the IgE and IgG responses to pieryI chloride are initiated in the lymph nodes and then develop in the spleen. IgE and IgG antibody production are both T-ceil dependent but not influenced by adult thymectomy. [ABSTRACT FROM AUTHOR]

Mice painted with the contact sensitizing agent picryl chloride produce IgG and reaginic or IgE-type antibody. They concomitantly produce suppressor cells which can inhibit IgG responses of normal mice to picryl chloride. These cells were produced between 3 and 7 days after primary sentitization (skin painting) and were T cells, as evidenced by their sensitivity to anti-θ serum and by their passage through nylon wool columns. Although they inhibited IgG responses they did not significantly change IgE titres. This correlates with a previous observation that repeated painting with picryl chloride increased IgE and not IgG responses. [ABSTRACT FROM AUTHOR]

Lymphocytes from mice immunized by painting with the contact sensitizing agent picryl chloride have been shown to produce regulatory effects on the DNA synthesis and contact sensitivity responses of normal mice painted with picryl chloride. This report describes the effect of these cells on antibody responses of normal mice to picryl chloride. Lymph node cells taken 5-7 days after painting increased early IgM antibody responses of normal mice to picryl chloride. Spleen cells were not effective. The increase was mediated by T cells as judged by anti-θ treatment and nylon wool filtration and could not be produced by killed, irradiated or allogeneic cells. A similar activity could be demonstrated in cells from mice painted with another contact sensitizing agent, oxazolone. The effect was strictly specific and cells from mice painted with picryl chloride or oxazolone would only increase responses to picryl chloride or oxazolone, respectively, even when presented with a mixture of the two antigens. The cells increasing antibody production were different from T cells previously shown to mediate contact sensitivity and T cells shown to regulate DNA synthesis in that they could not be generated in adult-thymectomized mice. [ABSTRACT FROM AUTHOR]

In the T suppressor circuit which affects contact sensitivity, the T acceptor cell trace) armed with T suppressor factor (TsF) and then triggered by antigen and major histocompatibility complex products (I-J) releases non-specific inhibitor (nsINH). These non-specific inhibitor(s) affect both the efferent and afferent stage of the contact sensitivity reaction and were originally detected by the inhibition of the passive transfer of contact sensitivity. The nsINH also blocks the induction of contact sensitivity when given intravenously at the time of immunization but has no effect when given at the time of challenge. Similarly, it blocks proliferation in the regional lymph nodes induced by contact sensitizer in a dose-dependent fashion; it acts when given at the time of immunization but not 1 day later. This effect is antigen non-specific and H-2 unrestricted. The nsINH bears I-J determinants as shown by affinity chromatography on monoclonal antibody. The nsINH comes from the Tacc and is not a breakdown product of the TsF. This is shown by the fact that, when the Tacc and TsF have I-J of different genotypes, the genotype of the nsINH corresponds to that of the Tacc. Parallel measurements of inhibition of lymphoproliferation and of passive transfer show that the nsINH has a molecular weight of 50-60 Kd and a pi around 6.8 and suggest that similar or identical molecules block both the afferent and efferent stage of the contact sensitivity reaction. [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]

Erythrocyte autoantibodies can be elicited in mice by injections of rat RBC which are cross-reactive with mouse RBC. This report shows that reduction of autoantibodies is dependent, in part, on gene(s) outside the H-2 complex. Using CBA mice congenic for Ig allotype and the F1 and F2 hybrids, a higher incidence of autoantibody production was observed in mice bearing the Ig allotype 1b (1bb' or 1ab) in contrast to mice homozygous for the allotype Ig-1a. Serum haemagglutination titres against rat RBC were not reduced in the groups of mice with the lower incidence of autoantibody production. A probable explanation for these observations is that the change in Ig allotype is associated with some change in the variable region determining autoimmune specificity that is governed by VH genes linked to allotype genes. The transfer of 30× 106 spleen cells from Coombs' positive mice to syngeneic recipients before starting the immunization regime with rat RBC suppressed autoantibody production and enhanced antibody production against rat RBC. These suppressor cells were effective in congemic mice and in F1 hybrids, which suggest that the Ig allotype is not a crucial site for the effector stage of suppression of this autoimmune response. [ABSTRACT FROM AUTHOR]

Mast cells from the peritoneum of mice painted with the contact sensitizing agent picryl chloride degranulate when exposed to antigen (TNP) in vitro. Degranulation was consistently demonstrated 4 days after painting which associated with the ability of mice to produce contact sensitivity reactions as measured by ear swelling and radiometric assays. Serum reagin or reagin-producing cells could not be detected until 6 days after painting but TNP-phage neutralizing activity was detected after 2 days. Mast cell degranulation could be elicited by TNP or DNP derivatives indicating the involvement of antibody. [ABSTRACT FROM AUTHOR]