The Journal of Immunology, Vol 157, Issue 7 2873-2882, Copyright © 1996 by American Association of Immunologists

ARTICLES

Extrathymic origin of human gamma delta T cells during fetal development

LD McVay and SR Carding
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

We have identified the first TCRs to be generated in vivo during normal human fetal development. Before thymic formation, the liver is a site of generation for a subset of V gamma 9/V delta 2+ gamma delta T cells. Analysis of the expression of the male-specific gene, SRY, by V gamma 9/V delta 2+ gamma delta T cells isolated from the fetal liver of male donors has shown that these cells are generated de novo in the liver. Examination of TCR-V gamma and -V delta gene expression demonstrated that although multiple receptor rearrangements could be detected, V gamma 9-JP- and V delta 2-D delta 3-J delta 1/3-encoded receptors were preferentially expressed in each of five individual liver samples. Structural analysis of these receptor chains and those expressed by a panel of V gamma 9/V delta 2+ fetal T cell clones showed that the V gamma 9-JP receptors were invariant or canonical and that the delta- chains contained non-germ line-encoded structural motifs. gamma delta T cells expressing these structurally limited receptor chains were shown to be functional and capable of responding to mycobacterial Ags. Together with the observation that V gamma 9/V delta 2+ cells represented the majority of T cells present in the fetal liver between 7 and 11 wk of development, our findings demonstrate that this subset of gamma delta T cells is a major, and presumably important, component of the human fetal immune system.

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