LPS REGULATION OF THE IMMUNE RESPONSE: CELLULAR AND MOLECULAR BASIS OF ADJUVANTICITY AND THE ROLE OF SUPPRESSOR T CELLS ON HOST RESPONSES

Abstract

LPS exerts several effects on lymphoid cells and the time of exposure is critical in determining whether augmentation or suppression of the host's immune response will be manifested. If appropriate doses of endotoxin are administered with antigen the well characterized adjuvant response is seen. We have evaluated the contribution of macrophages (MØ) and T cells and certain of their mediators to adjuvanticity by utilizing LPS responsive (C3H/HeN and C57BL/10 Sn) and nonresponsive (C3H/HeJ and C57BL/10 ScN) mice. Purified T and B spleen cells were obtained by glass and nylon wool column chromatography, while MØ were obtained from irradiated (1000 R) spleen cells. Appropriate mixtures of either LPS responsive or nonresponsive cells were cultured with either haptenated or normal heterologous erythrocytes and LPS. Adjuvanticity was obtained only when LPS responsive MØ and T cells (from either C3H/HeN or C57BL/10 Sn spleen) were cultured with B cells from either responder or nonresponder animals. Lymphocyte activating factor (LAF) (Interleukin 1, IL 1) plus LPS gave higher anti-SRC plaque forming cell (PFC) responses only in the presence of T cells from LPS responsive mice. Further, antigen-induced and LPS augmented PFC helper factor gave anti-SRC PFC responses in nonresponsive nude (C57BL/10 ScN) spleen cell cultures, suggesting that LPS induced adjuvanticity may be mediated by increasing the production of LAF (IL 1) and PFC helper factor. We have also investigated the role of suppressor T cells on immunogenic and mito-genic responses to LPS. Evidence is provided that significant suppression of lipid A effects is manifested by gut-associated-lymphoid tissue T cells, indicating that the normal Gram negative gut flora induces a cell population which can regulate B cell responses to bacterial endotoxin.