Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic involution - 1. Alterations in the CD4/CD8 distribution in thymocytes

We have previously shown that the progressive ascitic growth of a transplan table T cell lymphoma of spontaneous origin in a murine host, designated as Dalton's lymphoma (DL), induces the inhibition of various immune responses . in a quest to understand the mechanism(s) of tumor-growth-dependent immun osuppression, we were interested to investigate if the thymus, the center f or the differentiation of immunocompetent T cells, undergoes any alteration concomitant with the growth of DL. Thus, DL was grown as an ascitic tumor in BALB/c mice for a period of 4 or 17 days, designated as the early and la te tumor stages, respectively, and the thymuses were examined immediately a fter sacrifice of the animals on the 4th or 17th day of tumor transplantati on. Progressive growth of DL was observed to be associated with thymic atro phy, as well as an involution of thymic organization and a depletion of cel l mass. Histological sections of thymus from DL-bearing mice revealed a com plete disintegration of the thymic architecture with a massive depletion of the cortical region and disappearance of the corticomedullary junctions. F low cytometric analysis of alterations in the distribution of thymocytes re vealed a decrease in CD4+CD8-, CD4-CD8+ and CD4+CD8+ cell populations, wher eas the CD4-CD8- population showed an increase, suggesting an impairment in thymocyte differentiation at an early T cell maturation stage. Furthermore , tumor growth was shown to suppress the proliferation ability of thymocyte s. Moreover, an increase in thymocytes of smaller size was also found with the progression of DL, which is an indication that a large fraction of thym ocytes of a small, abnormal size could be apoptotic cells. Furthermore, the paper discusses the immunological implications of thymic atrophy in a host bearing a T cell lymphoma. Copyright (C) 2000 S. Karger AG, Basel.