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The Journal of Immunology, 2003, 170: 4087-4094.
Copyright © 2003 by The American Association of Immunologists

Distinct Requirements for IL-7 in Development of TCR{gamma}{delta} Cells During Fetal and Adult Life1

Karen Laky2,*, Julia M. Lewis{dagger}, Robert E. Tigelaar{dagger} and Lynn Puddington3,*

* Department of Medicine, Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and {dagger} Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520

TCR{gamma}{delta}-transgenic IL-7-/- mice were generated to determine whether T cells containing productively rearranged TCR{gamma}{delta} genes have additional requirements for IL-7 within the thymus or peripheral lymphoid tissues. Differences in developmental requirements for IL-7 by TCR{gamma}{delta} cells were noted and were linked to derivation from fetal- vs adult-type precursors in the thymus. Although TCR{gamma}{delta} cells are absent from IL-7-/- mice, TCR{gamma}{delta} cells were restored to the thymus and periphery by expression of TCR{gamma}{delta} transgenes. Endogenous TCR{gamma} chains were expressed by IL-7+/- but not IL-7-/- TCR{gamma}{delta}-transgenic mice, providing direct support for findings that IL-7 is necessary for rearrangement and expression of TCR{gamma} genes. The number of TCR{gamma}{delta} thymocytes was 10-fold reduced in TCR{gamma}{delta}-transgenic IL-7-/- embryos; however, adult TCR{gamma}{delta}-transgenic IL-7-/- or IL-7+/- mice had similar numbers of fetal thymus-derived TCR{gamma}{delta} cells in their skin. Thus, fetal TCR{gamma}{delta} cells required IL-7 for TCR rearrangement, but not for proliferation or survival in the periphery. In contrast, the numbers of TCR{gamma}{delta} cells in other tissues of TCR{gamma}{delta}-transgenic IL-7-/- mice were not completely restored. Moreover, coincident with the transition from the first to second wave of T cell precursors maturing in neonatal thymus, thymus cellularity of TCR{gamma}{delta}-transgenic IL-7-/- mice dropped significantly. These data indicated that in addition to TCRV{gamma} gene rearrangement, TCR{gamma}{delta} cells differentiating from late fetal liver or adult bone marrow precursors have additional requirements for IL-7. BrdU incorporation studies indicated that although IL-7 was not required for TCR{gamma}{delta} cell proliferation, it was required to prolong the life span of mature TCR{gamma}{delta} cells.




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