We have developed a human T lymphocyte hybridoma producing an immunosuppressive lymphokine. The lymphokine has been termed HSF for hybridoma suppressor factor. It appears to be a unique lymphokine based on both its biochemical and functional properties. HSF mediates the suppression of antibody production by normal human peripheral blood mononuclear leukocytes and also inhibits interleukin 2 (IL2) production by T lymphocytes. Our previous studies indicate that HSF suppresses immunoglobulin production by inhibiting the levels of IL2 in the lymphocyte cultures and thus interfering with the differention of B lymphocytes. In this application we propose to investigate whether HSF is selectively interfering with IL2 production, as our recent studies suggest, or whether HSF acts somewhat like cyclosporin A, downregulating lymphokine production in general. To approach this question we will monitor the effect of HSF on the production of several lymphokines and protein products of human T lymphocytes. These include IL4, IL5, IL6, gamma interferon, and the IL2 receptor. If HSF selectively inhibits IL2 production we propose to study the mechanisms involved in selective immunosuppression. Another aim of this grant is to determine the biochemical composition of HSF we plan to achieve this by pursuing the molecular isolation of HSF and to attempt to clone the gene for HSF. Preliminary studies indicate that it is a polypeptide of approximately 6,000 daltons. We plan to purify HSF to homogeneity, to sequence its amino acids and to clone the cDNA for HSF in an expression vector. To aid in these and other studies we are presently in the process of preparing monoclonal antibodies to HSF. These studies will greatly enhance our knowledge of what HSF is, how it mediates immunosuppression in vitro and will give us an indication of its potential as an immunotherapeutic agent in transplantation and autoimmunity.
| Haghighi, A Z; Cathcart, M K (1992) Subtractive antibody to a human immunosuppressive lymphokine affinity isolates a suppressive factor and blocks its function. Immunopharmacology 24:65-76 |
| Tomita, Y; Lieberman, B Y; Cathcart, M K (1990) Selective suppression of lymphokine production by human hybridoma suppressor factor (HSF). Immunobiology 181:64-83 |
