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

The common cytokine receptor gamma chain (gamma(c)), 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 gamma(c) is associated with alterations of intrathymic and peripheral T cell selection, we have analyzed gamma(c)-deficient mice made transgenic for the male-specific T cell receptor (TCR) HY (HY/gamma(c)(-) mice). In HY/gamma(c)(-) male mice, negative selection of autoreactive thymocytes was not diminished; however, peripheral T cells expressing transgenic TCR-alpha and -beta chains (TCR-alpha(T)/beta(T)) were absent, and extrathymic T cell development was completely abrogated. In HY/gamma(c)(-) female mice, the expression of the transgenic TCR partially reversed the profound thymic hypoplasia observed in nontransgenic gamma(c)(-) mice, generating increased numbers of thymocytes of all subsets, particularly the TCR-alpha(T)/beta(T) CD8(+) single-positive thymocytes. Despite efficient positive selection, however, naive CD8(+) TCR-alpha(T)/beta(T) T cells were severely reduced in the peripheral lymphoid organs of HY/gamma(c)(-) female mice. These results not only underscore the indispensible role of gamma(c) in thymocyte development, but also demonstrate the critical role of gamma(c) in the maintenance and/or expansion of peripheral T cell pools.