Impairment of T-cell functions with the progressive ascitic growth of a transplantable T-cell lymphoma of spontaneous origin

It has been observed that the progressive ascitic growth of a transplantabl e T-cell lymphoma of spontaneous origin, designated Dalton's lymphoma (DL), in a murine host induces inhibition of various immune responses and is ass ociated with an involution of thymus accompanied by a massive depletion of the cortical region and alteration in the distribution of thymocytes caused by tumour serum-dependent induction of apoptosis with a decrease of CD(4+) CD8(+), CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. Here, we report that thym ocytes of DL-bearing mice are defective in their proliferative ability and in their response to non-specific mitogenic stimulus in vitro. Also, antige n-specific T-cell proliferative ability representing the fundamental T-H fu nction declines under DL-bearing conditions and upon treatment with serum o f DE-bearing mice. Moreover, a significant inhibition of T-cell cytolytic a ctivity with a decreased ability to produce interferon gamma is shown by th e T cells of DE-bearing mice and by the T cells treated with DL-ascitic flu id, DL-conditioned medium or serum of DL-bearing mice. Further, addition of interleukin-2 and anti-interleukin-10 to the cultures of thymocytes treate d with serum of DL-bearing mice is found to inhibit the induction of apopto sis in thymocytes, a phenomenon associated with the progression of DL growt h. Analysis of the results indicates an immune deviation with the predomina nce of a T-H2-type response with the progression of tumour. We further disc uss the possible mechanisms that may explain the observed tumour-induced di minution of T-cell immunity. (C) 2000 Federation of European Microbiologica l Societies. Published by Elsevier Science B.V. All rights reserved.