EXOGENOUS AND ENDOGENOUS ANTIGENS ARE DIFFERENTIALLY PRESENTED BY MAST-CELLS TO CD4(-LYMPHOCYTES() T)

In the present work, we explored the cytokine-dependent regulation of bone marrow-derived mast cell (BMMC) antigen-presenting cell (APC) fun ction, and co-stimulation requirements, and analyzed the nature of ant igens presented to T cells. We observed an up-regulation of the APC fu nction of mast cells induced by granulocyte/macrophage-colony-stimulat ing factor (GM-CSF) and a complete abrogation by interferon (IFN)-gamm a. Expression of co-stimulatory molecules CD80 and CD86 was suggested by the ability of mast cells to activate purified lymph node-derived T cells. Indeed, addition of the fusion protein mCTLA4-Ig strongly inhi bited antigen presentation by mast cells to normal T cells and to the T cell hybridoma 3DO-54.8. The regulatory mechanisms of APC function b y GM-CSF and IFN-gamma were investigated by measuring CD80 and CD86 tr anscripts in mast cells. GM-CSF-treated mast cells showed a strong inc rease in the expression of both CD80 and CD86 transcripts, whereas in IFN-gamma-treated mast cells, this expression was completely abrogated . Thus, up- and down-regulation of CD80 and CD86 expression by GM-CSF and IFN-gamma is directly correlated to the APC function. In addition, we analyzed antigen presentation by mast cells of endogenous self-ant igens. Mast cells failed to activate anti-I-A or anti-I-E-specific T c ell hybridomas and alloreactive T cells in primary mixed lymphocyte re actions (MLR). Furthermore, mast cells did not present the mouse beta 2-microglobulin (m beta 2-m) peptide 25-40, constitutively expressed o n B cells. However, mast cells, especially those treated with GM-CSF, activated an anti-m beta 2-m-specific T cell hybridoma in the presence of exogenous peptide. The minor lymphocyte-stimulating antigen-1 Mls- 1(a) is a viral superantigen (vSAG) encoded by the the mouse mammary t umor provirus-7 (MMTV-7). Mast cells, despite a reasonable amount of m ajor histocompatibility complex class II on the cell surface and the p resence of MMTV transcripts predicted to encode the vSAG, cannot stimu late in vivo or in vitro V beta 6(+) T cells specific for Mls-1(a). In contrast, mast cells could present the exogenous bacterial SAG, staph ylococcal enterotoxin B (SEE), to specific V beta 8(+) T cells. The se lective ability of mast cells to present exogenous antigens may have p hysiological relevance in that mast cells could participate in immune response regulatory mechanisms by discriminating self from nonself.