The role of IL-7 in thymic and extrathymic development of TCR gamma delta cells.
IL-7-deficient (IL-7(-/-)) mice have reduced numbers of B and TCR alpha beta cells, but lack mature TCR gamma delta cells. Although most T cell development occurs in the thymus, some intestinal intraepithelial lymphocytes (IEL), including TCR gamma delta cells, can develop extrathymically. Epithelial cells in both thymus and intestine synthesize IL-7, suggesting that TCR gamma delta cell development could occur in either site. To evaluate the role of thymic IL-7 in development of TCR gamma delta cells, newborn TCR beta-deficient (TCR beta(-/-)) thymi were grafted to IL-7(-/-) mice. Donor- and host-derived TCR gamma delta cells were recovered from thymus grafts, spleen, and IEL. However, when IL-7(-/-) thymi were grafted to TCR beta(-/-) mice, no development of graft-derived TCR gamma delta cells occurred, indicating that extrathymic IL-7 did not support TCR gamma delta IEL generation from newborn thymic precursors. In contrast, TCR gamma delta IEL development occurred efficiently in adult, thymectomized, irradiated C57BL/6J mice reconstituted with IL-7(-/-) bone marrow. This demonstrated that extrathymic development of TCR gamma delta IEL required extrathymic IL-7 production. Thus, intrathymic IL-7 was required for development of thymic TCR gamma delta cells, while peripheral IL-7 was sufficient for development of extrathymic TCR gamma delta IEL.
Department of Medicine, University of Connecticut Health Center, Farmington 06030, USA.
K
K
Laky
L
L
Lefrançois
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von Freeden-Jeffry
R
R
Murray
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L
Puddington
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D015851:Interleukin-7 / Q000378:metabolism / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D011828:Radiation Chimera; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin / Q000096:biosynthesis; D020395:Receptors, Interleukin-7; D013234:Stem Cells / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; D019009:Proto-Oncogene Proteins c-kit