Sequential stages of human T lymphocyte differentiation

Abstract

Induction of thymus-dependent (T) cell differentiation was performed in vitro with thymic factors as inducers. T cell precursors from human bone marrow first expressed surface differentiation antigens and then acquired the capacity to form rosettes with sheep erythrocytes. The latter marker could not be induced when cells with differentiation antigens were eliminated. The proliferative responses to phytomitogens or to allogeneic stimuli appeared to be characteristics of later stages in differentiation that can be induced or amplified by in vitro incubation of marrow cells or thymocytes with thymic factors. When phytomitogen-responsive cells from peripheral blood were inactivated in vitro, the allogeneic response was enhanced. Although these responses are acquired almost concomitantly, they are envisioned to be characteristics of separate T cell subsets. After immunological reconstitution of patients, the T cell development in vivo involves a succession of differentiation events similar to that described above. Experiments with mice, using similar methods, showed that graft-vs.-host inducing capacity is a function of a cell population distinct from that which yields a proliferative response to in vitro stimulation by phytohemagglutinin. There apparently is a sequential differentiation of human prothymocytes into various subsets of mature T cells.