Distinct requirements for IL-7 in development of TCR gamma delta cells during fetal and adult life.
TCRgammadelta-transgenic IL-7(-/-) mice were generated to determine whether T cells containing productively rearranged TCRgammadelta genes have additional requirements for IL-7 within the thymus or peripheral lymphoid tissues. Differences in developmental requirements for IL-7 by TCRgammadelta cells were noted and were linked to derivation from fetal- vs adult-type precursors in the thymus. Although TCRgammadelta cells are absent from IL-7(-/-) mice, TCRgammadelta cells were restored to the thymus and periphery by expression of TCRgammadelta transgenes. Endogenous TCRgamma chains were expressed by IL-7(+/-) but not IL-7(-/-) TCRgammadelta-transgenic mice, providing direct support for findings that IL-7 is necessary for rearrangement and expression of TCRgamma genes. The number of TCRgammadelta thymocytes was 10-fold reduced in TCRgammadelta-transgenic IL-7(-/-) embryos; however, adult TCRgammadelta-transgenic IL-7(-/-) or IL-7(+/-) mice had similar numbers of fetal thymus-derived TCRgammadelta cells in their skin. Thus, fetal TCRgammadelta cells required IL-7 for TCR rearrangement, but not for proliferation or survival in the periphery. In contrast, the numbers of TCRgammadelta cells in other tissues of TCRgammadelta-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 TCRgammadelta-transgenic IL-7(-/-) mice dropped significantly. These data indicated that in addition to TCRVgamma gene rearrangement, TCRgammadelta 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 TCRgammadelta cell proliferation, it was required to prolong the life span of mature TCRgammadelta cells.
Laky
Karen
K
Department of Medicine, Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Lewis
Julia M
JM
Tigelaar
Robert E
RE
Puddington
Lynn
L
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology*; D005260:Female; D019676:Genes, T-Cell Receptor delta / Q000276:immunology; D015851:Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta