Characterization of gamma/delta T cell clones isolated from human fetal liver and thymus

The origin and development of T cells bearing gamma/delta T cells receptors (TcR) has been extensively studied in the mouse. By contrast, little is known about development patterns and diversity of the human gamma/delta T cell lineage. To study the repertoire of human gamma/delta+ T cells during T cell ontogeny, we have isolated clonal populations of gamma/delta+ T cells from 14-week fetal thymus and liver and characterized the molecular composition of their TcR. The technique of in situ hybridization was used to identify cells expressing TcR genes in fetal liver and thymus. A panel of clones representative of developing T cell populations found in vivo was subsequently isolated from both tissues and clones expressing cell surface gamma/delta receptors were identified. Although both the liver-derived gamma/delta+ T cell clone, L2, and the thymus-derived gamma/delta+ T cell clone, T6, had similar cell surface phenotypes, namely CD3+, CD7+, CD45+ and CD8-, their reactivity with anti-CD2 and -CD4 antibodies was different. L2 was CD2high, CD4- whereas T6 was CD2low, CD4low. Both clones possessed effector functions similar to those of adult T cells as demonstrated by the synthesis and secretion of cytokines in response to stimulation through the CD3/TcR complex. Analysis of the TcR composition of the fetal clones showed both clones to possess similar or identical gamma chain components, C gamma 1, J gamma 1/2, V gamma 8, and both utilize V delta gene segments other than V delta 1. This TcR genotype has not been previously reported in the analysis of adult gamma/delta+ T cells. Our studies have identified a unique population of human gamma/delta+ T cells that may be derived extrathymically and appear to be preferentially and perhaps transiently expressed during fetal life.