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The Journal of Immunology, 2004, 172: 1637-1645.
Copyright © 2004 by The American Association of Immunologists

Ontogeny of {gamma}{delta} T Cells in Humans

Stephen C. De Rosa*, James P. Andrus{dagger}, Stephen P. Perfetto*, John J. Mantovani{ddagger}, Leonard A. Herzenberg{ddagger}, Leonore A. Herzenberg{ddagger} and Mario Roederer1,*

* Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892; and Departments of {dagger} Pediatrics and {ddagger} Genetics, Stanford University, Stanford, CA 94305

T cell receptors consist either of an {alpha}-chain combined with a {beta}-chain or a {gamma}-chain combined with a {delta}-chain. {alpha}{beta} T cells constitute the majority of T cells in human blood throughout life. Flow cytometric analyses presented in this study, which focus on the representation of the developmental (naive and memory) subsets of {gamma}{delta} T cells, show by function and phenotype that this lineage contains both naive and memory cells. In addition, we show that the representation of naive T cells is higher among {alpha}{beta} than {gamma}{delta} T cells in adults and that the low frequency of naive {gamma}{delta} T cells in adults reflects ontological differences between the two major {gamma}{delta} subsets, which are distinguished by expression of V{delta}1 vs V{delta}2 {delta}-chains. V{delta}1 cells, which mirror {alpha}{beta} cells with respect to naive representation, predominate during fetal and early life, but represent the minority of {gamma}{delta} cells in healthy adults. In contrast, V{delta}2 cells, which constitute the majority of adult {gamma}{delta} cells, show lower frequencies of naive cells than V{delta}1 early in life and show vanishingly small naive frequencies in adults. In essence, nearly all naive V{delta}2 cells disappear from blood by 1 year of life. Importantly, even in children less than 1 year old, most of the nonnaive V{delta}2 cells stain for perforin and produce IFN-{gamma} after short-term in vitro stimulation. This represents the earliest immunological maturation of any lymphocyte compartment in humans and most likely indicates the importance of these cells in controlling pathology due to common environmental challenges.




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