SummaryT-lymphocyte activation triggered by anti-CD3, endogenous or exogenous superantigen, and mitogens was suppressed in a cell-dose-dependent fashion by peritoneal cavity (PerC) leucocytes. Study of lymphocyte-deficient mice and the use of multiparameter fluorescence-activated cell sorter analyses revealed that macrophages were responsible for this form of immune regulation. Interferon-c was essential to trigger suppression, which, by enzyme inhibition studies, was shown to be the result of tryptophan and arginine catabolism. These results illustrate that macrophages, which are classically defined by their innate effector function as antigen-presenting cells, have the potential to temper adaptive immunity.

SUMMARYThe B lymphocyte subsets of X-chromosome-linked immune-de®cient (XID) mice were examined by¯ow cytometric analyses of spleen and peritoneal cells. As shown in prior studies, young adult XID mice had reduced representation of the CD5 (B-1a) subset in their peritoneal cavity. However, the CD11b (B-1b) B-cell subset was present and exhibited the IgM hi CD45 lo CD23À phenotype characteristic of most B-1 cells. Although present at a lower frequency than that found in their normal counterparts, B-1b cells were evident in CBA/N and (XD2J)F 1 male mice. With increasing age, B-1b cell number increased and in the oldest XID mice were present as B-cell chronic lymphocytic leukaemia. These results show that XID mice do have B-1 cells, particularly the B-1b subset.

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High Mφ:T cell ratios suppress the immune response to the retroviral superantigen Mls by IFNγ-triggered production of the arg- and trp-consuming enzymes iNOS and IDO. Attempts to reverse suppression by treatment with pro-inflammatory cytokines revealed that IL-6 improved the T cell response to Mls and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mφ expression of CD80, a ligand for the immune suppressive B7H1 and CTLA-4 receptors. These results illustrate potential strategies for reversing the suppression of cell-mediated immunity characteristic of the high Mφ:T cell ratios found in many tumors.

Components of the immune system essential for curbing tumor progression are often found within the tumor. High macrophage to T cell ratios (Mö:T) are hallmarks of the tumor microenvironment. We have shown that such conditions suppress the immune response to the retroviral superantigen Mls by IFN ã -triggered production of the Arg- and Trp-consuming enzymes iNOS and IDO. In attempts to reverse suppression by treatment with pro-inflammatory cytokines, IL-6 improved the T cell response to Mls, IL-1 and TNFá had little effect, and the pro-hematopoietic cyokines IL-3 and GM-CSF increased suppression. GM-CSF treatment increased Mö expression of CD80, a significant ligand for the immunosuppressive B7H1 and CTLA-4 receptors. These results reveal avenues for reversal of the suppression of cell-mediated immunity characteristic of the high Mö:T cell ratios found in many tumors. Supported by NIH AREA R15-AI060356-01.