Delayed maturation of CD4-CD8- FcγRII/III+ T and natural killer cell precursors in FcεRIγ transgenic mice

Abstract

FcεRIγ (γ) is a member of a group of related proteins (the ζ-family dimers) that function as signal-transducing components of both Fc receptors and the T cell antigen receptor (TCR). Analysis of γ expression during fetal thymus ontogeny revealed that it is expressed in early thymocytes, before the initiation of clonotypic TCR-α and TCR-β gene rearrangement but is down- regulated in most adult thymocytes. To explore a possible role for γ in the thymocyte development, we generated transgenic mice in which this protein was overexpressed at all stages of ontogeny. Overexpression of γ inhibited the maturation of T cells as well as natural killer (NK) cells. The developmental effects were transgene dose related and correlated with markedly delayed maturation of fetal CD4 CD8 FcRII/III+ thymocytes, cells thought to include the progenitors of both T and NK cells. These results suggest that the ζ and γ chains serve distinctive functions in thymocyte development and indicate that Fc receptor(s) may play an important role in regulating the differentiation of early progenitor cells within the thymus.