Immunopotentiation in mice bearing a spontaneous transplantable T-cell lymphoma: role of thymic extract.

ABSTRACT

Progressive ascitic growth of a spontaneous transplantable T-cell lymphoma, designated as Dalton's lymphoma (DL), in a murine host has been shown to be associated with an involution of thymus accompanied by a massive depletion of the cortical region and an alteration in the distribution of thymocytes by a decrease of CD4+CD8+, CD4+CD8- and CD4-CD8+ phenotypes caused by an enhanced induction of apoptosis in thymocytes. Moreover, an inhibition of humoral and cell mediated immune responses involving non-specific as well as antigen-specific T cell proliferative and cytolytic abilities with a decrease in the production of interferon gamma (IFNg) by the T cells of DL bearing mice has been observed. Results of the present study show that the administration of total thymic extract (TE) in DL bearing mice results in an increased survival of the DL bearing mice alongwith a significant increase in the weight of thymus and the total number of thymocytes with a lesser number of percent apoptotic thymocytes as compared to that in untreated DL-bearing mice. It is also shown that TE administration has a positive immunomodulatory effect on T cell functions as T cells obtained from TE administered DL bearing mice show an increased IFNg, production and an improved antigen specific proliferative ability. Moreover, the study indicates that TE acts directly on T cells as in an in vitro assay TE antagonised DL growth-associated induction of thymocyte apoptosis. Taken together, the results support the immunomodulatory function of the adult thymus and utilization of thymus derived factors as a potential immunotherapeutic agent for reversing tumor growth-associated immunosuppression.