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A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were.reactive with both OKT9 and OKT1O. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6, lost OKT9 antigen, and expressed reactivity with OKT4 and OKT5. These last two monoclonal antibodies were previously shown to define inducer (helper) and cytotoxic/suppressor populations, respectively, in peripheral blood. The OKT4+, OKT5+, OKT6+ "common" thymocyte population represents the majority of thymocytes and accounts for more than 70% of thymocytes. With further maturation, thymocytes lose OKT6 reactivity, segregate into OKT4+ and OKT5+ subsets, and acquire reactivity with OKT3 (and OKT1). This latter stage corresponds to the more functionally mature subset. The possible relationship of acute lymphoblastic leukemia of T-cell lineage to these proposed stages of intrathymic differentiation was determined. Analysis of25 tumor populations showed that 21 could be related to one or another differentiative stage. The majority (15/21) were derived from an early thymocyte or prothymocyte subpopulation, 5/25 were derived from a common thymocyte subpopulation, and 1/25 was derived from a mature (OKT3+) subpopulation. These data suggest that is it now possible to define stages of T-cell differentiation that can be related to T-cell malignancies in humans.The importance of a thymic microenvironment in the differentiation and functional maturation of T cells has been demonstrated in several species. Moreover, profound changes in cell-surface antigens mark the various stages of T-cell ontogeny (1-7). For (12). These thymcytes were the most functionally mature and probably ready for peripheral exportation. Human peripheral T cells also consist of functionally distinct subsets (13)(14)(15)(16)(17)(18)(19).In the present study, we used a series of monoclonal antibodies reactive selectively with subpopulations of human thymocytes and inducer and suppressor T-cell subsets in order to further define stages of thymic differentiation (18, 19). We show that three major stages of intrathymic differentiation exist and that the majority of tumor populations from patients with acute lymphoblastic leukemia of T-cell lineage (T-ALL) can be shown to

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