Growth of murine thymocytes in vitro in chemically defined medium

Immature T cells proliferate, diversify their repertoire of antigen specificity, are selected for MHC-restricted function, are selected for non-self reactivity and undergo maturation in the thymus. The mechanisms underlying thymic development are poorly understood. One reason for this is that murine thymocytes generally die when cultured in vitro under conditions which normally support lymphocyte growth. We describe conditions under which CD4-CD8- thymocytes proliferate at a high rate and acquire maturation-associated markers in vitro in the absence of exogenous mitogenic stimuli. CD4+CD8- cells also multiplied in the absence of added lymphokines while CD4-CD8+, but not CD4+CD8+, cells proliferated in the presence of exogenous IL-2. Proliferation of CD4-CD8- cells was associated with production of both IL-1 and IL-2. Proliferation of unfractionated, CD4-CD8- and CD4+CD8- thymocytes was dependent upon interaction of IL-2 with its receptor. CD4-CD8- cells acquired CD4 and/or CD8 markers during culture, indicating that, in addition to the proliferation, some maturation occurred. Proliferation occurred in complexes containing one or more central stromal cells. The results are discussed in relation to their possible relevance to thymocyte development.