Functional characterization of human T lymphocyte subsets distinguished by monoclonal anti-Leu-8

Previous studies have shown that monoclonal anti-Leu-8 antibody identifies functionally distinct subpopulations within both the Leu-2 (T8⁺) and Leu-3 (T4⁺) lineages of human T lymphocytes. We now report in detail on the tissue distribution of the Leu-8 and on extensive functional studies of T cell subsets distinguished by their expression or lack of expression of this marker. Leu-8 is present on a wide variety of hematologic cells, including granulocytes, T and B lymphocytes, monocytes, and null or NK cells. Within lymph nodes and tonsils, Leu-8 is absent from both B and T cells within germinal centers but is present on nearly all paracortical lymphocytes. Leu-8 is present on most but not all EBV-transformed B cell lines, reflecting its presence on a subset of normal peripheral blood B cells. None of six malignant T cell lines tested were Leu-8⁺, whereas most circulating T cells are Leu-8⁺. Although standard immunoprecipitation techniques failed to demonstrate any specific bands on SDS polyacrylamide gels, the antigenic determinant recognized by anti-Leu-8 is protein or protein-associated, because brief treatment of target cells with pronase abrogated binding of anti-Leu-8. Both Leu-3⁺8⁺ and Leu-3⁺8^- cells proliferated in response to several soluble antigens and to autologous and allogeneic non-T cells. Nevertheless, nearly all of the helper T cells for PWM- and AMLR-induced PFC were contained within the Leu-3⁺8^- subset. Optimal supression of the PWM-induced PFC response required both Leu-2⁺8⁺ and Leu-2⁺8^- cells, and irradiation of either subset with 3000 R abrogated the capacity of the recombined subsets to effect suppression. In contrast to help for B cell differentiation, both Leu-3⁺8⁺ and Leu-3⁺8^- cells were capable of amplifying the development of allospecific T killer cells; precursor and effector T killer cells could be found within both Leu-2⁺8⁺ and Leu-2⁺8^- subpopulations. The correlation between Leu-8 phenotype and selected immune functions of T cells (and B cells; see companion paper) indicates that anti-Leu-8 distinguishes important immunoregulatory T and B lymphocyte subsets in man.