Characterization of γ/δ T cell clones isolated from human fetal liverand thymus

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Abstract
The origin and development of T cells bearing γ/δ T cell receptors (TcR) has been extensively studied in the mouse. By contrast, little is known about development patterns and diversity of the human γ/δ T cell lineage. To study therepertoire of human γ/δ+ T cells during T cell ontogeny, wehave isolated clonal populations of γ/δ+ T cells from 14‐week fetal thymus and liver and characterized the molecular compositionof 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 γ/δ receptors were identified. Although both the liver‐derived γ/δ+ T cell clone, L2, and the thymus‐derived γ/δ+ 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 γ chain components, Cγ1, Jγ1/2, Vγ8, and both utilize Vδ gene segments other than Vδ1. This TcR genotype has not been previously reported in the analysis of adult γ/δ+ T cells. Our studies have identified a unique population of human γ/δ+ T cells that may be derived extrathymically and appear to be preferentially and perhaps transiently expressed during fetal life.