Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions.

Abstract

Alloreactive human T lymphocytes were cloned in soft agar or by limiting dilution and subsequently propagated with interleukin 2 and alloantigen for .gtoreq. 8 mo. By indirect immunofluorescence every clone was reactive with anti-Ia antibodies and the T cell-specific antibodies anti-T3 and anti-T11 and expressed either T4 or T8 antigens. All 15 T8+ clones were highly cytotoxic for the sensitizing alloantigen. Only 2 of 7 T4+ clones mediated cytotoxic effector function. The specificity of T8+ clones and subclones was analyzed on a panel of typing cells and by antibody blocking studies of major histocompatibility complex (MHC) determinants on the stimulating alloantigen. T8+ clones killed targets that shared class I MHC antigens (HLA-A,B) with the original stimulator cells, cytotoxic T4+ clones were directed at class II MHC antigens (Ia-related). Preincubation of the allogeneic target cell with a monoclonal antibody to a nonpolymorphic HLA .alpha.-chain determinant inhibited killing by the T8+ clones but did not affect T4+ cytotoxic function. In a reciprocal fashion, anti-Ia antibodies to common framework structures on the same target cell blocked killing by T4+ but not by T8+ clones. T4+ and T8+ T lymphocytes apparently have receptors for different classes of MHC antigens and cytotoxic T4+ subpopulations might be important in human transplantation and autoimmune disorders.