Critical role for the common cytokine receptor gamma chain in intrathymic and peripheral T cell selection

• Published in: The Journal of experimental medicine 1996-03, Vol.183 (3), p.1111-1118
• Main Authors: DiSanto, J P, Guy-Grand, D, Fisher, A, Tarakhovsky, A
• Format: Article
• Language: English
• Subjects: Animals; CD4-Positive T-Lymphocytes; Cells, Cultured; Crosses, Genetic; Duodenum - immunology; Female; Flow Cytometry; Lymphocyte Activation; Macromolecular Substances; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Cytokine - chemistry; Receptors, Cytokine - immunology; Receptors, Interleukin-2 - genetics; Spleen - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.183.3.1111

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.