This is a proposal to study the cellular and biochemical mechanism of the myeloma tumor cell suppression mediated by the host isotype-specific suppressor T cells with Fc receptors that are found in mice and patients with multiple myeloma. We have previously shown that mice and patients with multiple myeloma develop an extraordinary increase in circulating T cells with surface receptors for the Fc portion of immunoglobulin molecules. In addition, we have shown that these Fc receptor-bearing T cells are isotype-specific suppressor cells in normal immune response models. Recent studies have shown that T cells with IgA-Fc receptors, acting through a soluble factor, can suppress both the growth and secretion of IgA myeloma tumor cells. Since the exact mechanism of this suppression is unknown, we herein propose to utilize an IgA murine myeloma model to: 1) establish if T cell-T cell or T cell-macrophage interactions are necessary for this response, 2) establish if the major histocompatibility gene complex or the immunoglobulin heavy chain gene complex are important in controlling this response, 3) characterize biochemically the soluble suppressor factor produced by T cells with IgA-Fc receptors and, 4) characterize the kinetics and biochemical events associated with myeloma cell suppression. In addition, in order to establish the generality of this response,we will extend out studies with murine IgA myeloma to study: 5) the effects of Fc-receptor-bearing T cells on IgG and IgM murine myeloma, and 6) the effects of Fc-receptor-bearing T cells on human myeloma tumor cells in vitro. Since Fc-receptor-bearing T cells can suppress myeloma tumor cell growth, information obtained from the above proposed studies might ultimately be exploited clinically in the treatment of patients with multiple myeloma or other tumors of B cell origin, such as leukemia or lymphoma.
