CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE : IX. REGULATION OF HAPTEN-SPECIFIC ANTIBODY CLASS BY CARRIER PRIMING

Mice primed to horse erythrocytes (HRBC) produced greatly enhanced 3,5-dinitro,4-hydroxyphenylacetic (NNP)-specific indirect plaque-forming cell (7S PFC) responses when given NNP.HRBC but no difference in hapten-specific direct (19S PFC) responses in comparison to non-carrier-primed mice. The effect was carrier specific and could not be produced by simultaneous challenge of rabbit erythrocyte (RRBC)-primed mice with RRBC and NNP.HRBC. When spleen cells from HRBC-primed mice were transferred to irradiated recipients, there was again an enhanced 7S response to NNP.HRBC. The primed spleen cells could be replaced by giving activated thymus cells to HRBC together with normal spleen as a source of B cells. It is concluded that T cells influence not only the amount but also the class of antibody formed by hapten-sensitive B cells

Generalized Immunological Decline during Long-Term Experimental Infection with Mycobacterium avium

Terminal loss of immune responsiveness in C57BL/10 mice intranasally infected with Mycobacterium avium was observed in both spleen and lung. It was nonspecific and related to the duration of infection, not the age of the mice. While there was loss of total T cells, the remaining cells were less efficient at gamma interferon production

Polyadenylic acid-polyuridylic acid (poly A:U) and experimental murine brucellosis: II. Macrophages as target cells of poly A:U in experimental brucellosis

Results of in vivo and in vitro experiments suggest that the early suppression of brucella growth in double stranded polyadenylic-polyuridylic acid-(poly A:U-) treated mice was due to a non-specific activation of macrophages by poly A:U. Poly A:U administered intraperitoneally at the time of brucella infection failed to enhance T-cell mediated responses to the organism, namely delayed-type hyper-sensitivity to brucellin and adoptive transfer of immunity to the infection. Poly A:U did not augment the protective antibodies formed in response to infection. Although poly A:U has been previously found to suppress brucellosis in athymic (nude) mice, it did not enhance the thymus-dependent antibody response to sheep erythrocytes in brucella-infected nudes, suggesting that it did not significantly enhance maturation of their helper T-cell percursors. Increased macrophage spreading, an indication of activation, was seen immediately after administration of poly A:U and Brucella abortus. Later on the infection spreading was suppressed, a phenomenon which appears to relate to the biphasic effect of poly A:U in vivo described in the accompanying paper. Peritoneal macrophages treated in vitro with poly A:U were stimulated to spread on plastic surfaces, even when T lymphocytes were removed with anti-Thy-1 serum and complement

Interleukin-2 and Loss of Immunity in Experimental Mycobacterium avium Infection

Experimental infection of mice with a virulent strain of Mycobacterium avium leads to a slowly progressive disease, which we have previously shown culminates in loss of gamma interferon (IFN-γ) production by T lymphocytes and death of the animals approximately 40 weeks after infection. Here we investigated the changes in T-cell activation, the production of interleukin-2 (IL-2), and the response to IL-2 throughout M. avium infection as a possible explanation for this loss. We found that there is a steady increase in the percentage of T cells expressing activation markers right to the end of infection. However, in vivo T-cell proliferation, measured as a percentage of CD4(+) and CD8(+) cells incorporating 5-bromo-2′-deoxyuridine, initially increased but then remained constant. In the final stages of infection there was a decline in proliferation of activated (CD62L(−)) T cells. Since IL-2 is a major driver of T-cell proliferation, we asked whether this was due to loss of IL-2 responsiveness or production. However, CD25 (IL-2Rα) continued to be highly expressed in the terminal stages of infection, and although IL-2 production declined, addition of recombinant IL-2 to cultures could not rescue the final loss of IFN-γ production