INTRATUMORAL ACTIVATION OF CD8-POSITIVE CYTOTOXIC LYMPHOCYTES IN ACQUIRED-IMMUNODEFICIENCY-SYNDROME LYMPHOMAS

The incidence of lymphomas is unusually high in human immunodeficiency virus (HIV)-infected patients. Because cytotoxic T lymphocytes (CTL) represent a major mechanism of the antitumoral immune response in immu nocompetent individuals, we asked whether intratumoral activation of C TL was impaired in acquired immune deficiency syndrome (AIDS) lymphoma s. Immunohistochemical experiments showed that in AIDS lymphomas intra tumoral CD8-positive T lymphocytes accumulated and expressed the TIA-1 antigen, a marker of cytotoxic cells. Flow cytometry studies and in s itu hybridization of lymphomatous tissue confirmed the differentiation of CD8-positive cells in cytotoxic cells and their activation, as ass essed by their expression of CD38 and human leukocyte antigen (HLA) DR markers as well as the perforin and granzyme B genes, which code for two molecules involved in target cell killing. On average, perforin-pr oducing cells were as numerous in AIDS lymphomas (5,647 +/- 2,655 cell s/cm(2)) as in lymphomas from immunocompetent individuals (3,294 +/- 1 ,544 cells/cm(2)). The density of activated CD8-positive cells in the 22 AIDS lymphomas tested was not correlated with peripheral CD4-positi ve cell counts. These results suggest that in AIDS lymphomas the steps of differentiation and activation of cytotoxic CD8-positive cells are not altered by immune deficiency and that they can take place through pathways relatively independent of CD4-positive T lymphocytes. Thus, other mechanisms of immune deficiency should account for the increased frequency of lymphomas in patients with AIDS. Copyright (C) 1995 by W .B. Saunders Company