Discrete stages of human intrathymic differentiation: Analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage

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Abstract
A series of monoclonal antibodies was used to define 3 discrete stages of human intrathymic T[thymus-derived]-cell differentiation. The earliest stage was confined to < 10% of thymocytes, which were reactive with OKT9 and OKT10. Subsequently, .apprx. 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6, lost OKT9 antigen, and expressed reactivity with OKT4 and OKT5. These last 2 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 > 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 of 25 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 it is now possible to define stages of T-cell differentiation that can be related to T-cell malignancies in humans.