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

Abstract

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

Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts

“…The observation that CD8 þ T cells expressing only HLA-DR but not CD38 are lost in Ethiopian AIDS patients is in agreement with a previous prospective study which demonstrated that the presence of this subset is associated with long-term survival and stable CD4 þ T cell counts [14]. Apart from being an activation marker, CD38 is also detected in immature cells [43].The representation of CD4 þ and CD8 þ T cells expressing only CD38 but not HLA-DR is increased in both HIV þ and AIDS groups compared with the HIV ¹ group. This observation may reflect that in HIV infection, apart from immune activation, there is also an increased flow of immature cells into the periphery due to accelerated destruction and replacement of mature T cells (see also [44]).…”

Immuno-histological diagnosis of lymphoproliferative diseases by selected combinations of antisera and monoclonal antibodies

“…Our results also confirm previous studies showing that in most cases of NHL a monoclonal LC expression of membraneassociated Ig (mlg; K or A) can be detected in frozen sections (Levy et al, 1977;Warnke & Levy, 1978) (Nathwani et al, 1978), w-hich reveals little about the malignant nature of the transformed tumour. Furthermore, the observations support previous reports (Habeshaw et al, 1979;Warnke & Levy, 1978) that in follicular (cent,roblastic-centrocytic) Further studies (with antibodies detecting T-cell subsets of helper and suppressor fuLnctions (Reinherz et al, , 1980) will reveal the clinical significance of these findings. Our data here show that these studies are technicallv feasible.…”

“…6). Other monoclonal antibodies reacting with T cells , T-cell subsets (Reinherz et al, , 1980, B cells and B cell subsets (Brooks et al, 1980) will further advance the immunological analysis of NHL, especially if used in appropriate combinations with other anitisera. The use of a panel of antibodies against B-cell subsets would be important, since the analysis of receptor profiles on these subsets already reveal remarkable (but not absolute) correlations with the histological pattern of NHL, and show prognostic significance (Habeshaw et al, 1979;Stein et al, 1978).…”

Immunophenotyping of acute leukemias and myelodysplastic syndromes

“…In addition to CD7 and cCD3, Pre-T ALL cases express surface CD2, CD5, and/or CD8. As cortical thymocytes (41), leukemic cells from cortical T-ALL display reactivity for CD1a. The TIV/mature T-ALL phenotype (sCD3ϩ, CD1aϪ, CD4ϩ, or CD8ϩ) is more often observed among patients presenting with T-lymphoblastic lymphomas than a pure T-ALL.…”