Critical role for the common cytokine receptor gamma chain in intrathymic and peripheral T cell selection.
The common cytokine receptor gamma chain (gammac), which is a functional subunit of the receptors for interleukins (IL)-2, -4, -7, -9, and -15, plays an important role in lymphoid development. Inactivation of this molecule in mice leads to abnormal T cell lymphopoiesis characterized by thymic hypoplasia and reduced numbers of peripheral T cells. To determine whether T cell development in the absence of gammac is associated with alterations of intrathymic and peripheral T cell selection, we have analyzed gammac-deficient mice made transgenic for the male-specific T cell receptor (TCR) HY (HY/gammac- mice). In HY/gammac- male mice, negative selection of autoreactive thymocytes was not diminished; however, peripheral T cells expressing transgenic TCR-alpha and -beta chains (TCR-alphaT/betaT) were absent, and extrathymic T cell development was completely abrogated. In HY/gammac- female mice, the expression of the transgenic TCR partially reversed the profound thymic hypoplasia observed in nontransgenic gammac- mice, generating increased numbers of thymocytes in all subsets, particularly the TCR-alphaT/betaT CD8+ single-positive thymocytes. Despite efficient positive selection, however, naive CD8+ TCR-alphaT/betaT T cells were severely reduced in the peripheral lymphoid organs of HY/gammac- female mice. These results not only underscore the indispensible role of gammac in thymocyte development, but also demonstrate the critical role of gammac in the maintenance and/or expansion of peripheral T cell pools.
DiSanto
J P
JP
Unité 429 Institut National de la Santé et de la Recherche Medicale, Hôpital Necker-Enfants Malades, Paris, France.
Guy-Grand
D
D
Fisher
A
A
Tarakhovsky
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004386:Duodenum / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D046911:Macromolecular Substances; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018121:Receptors, Cytokine; D015375:Receptors, Interleukin-2