The CD3γ chain is essential for development of both the TCRαβ and TCRγδ lineages

Abstract

CD3γ and CD3δ are the most closely related CD3 components, both of which participate in the TCRαβ- CD3 complex expressed on mature T cells. Interestingly, however, CD3δ does not appear to participate functionally in the pre-T-cell receptor (TCR) complex that is expressed on immature T cells: disruption of CD3δ gene expression has no effect on the developmental steps controlled by the pre-TCR. Here we report that in contrast with CD3δ, CD3γ is an essential component of the pre-TCR. We generated mice selectively lacking expression of CD3γ, in which expression of CD3δ, CD3ε, CD3ζ, pTα and TCRβ remained undisturbed. Thus, all components for composing a pre-TCR are available, with the exception of CD3γ. Nevertheless, T-cell development is severely inhibited in CD3γ-deficient mice. The number of cells in the thymus is reduced to < 1% of that in normal mice, and the large majority of thymocytes lack CD4 and CD8 and are arrested at the CD44-CD25+ double negative (DN) stage of development. Peripheral lymphoid organs are also practically devoid of T cells, with absolute numbers of peripheral T cells reduced to only 2-5% of those in normal mice. Both TCRαβ and TCRγδ lineages fail to develop effectively in CD3γ-deficient mice, although absence of CD3γ has no effect on gene rearrangements of the TCRβ, δ and γ loci. Furthermore, absence of CD3γ results in a severe reduction in the level of TCR and CD3ε expression at the cell surface of thymocytes and peripheral T cells. The defect in the DN to double positive transition in mice lacking CD3γ can be overcome by anti-CD3ε-mediated cross-linking. CD3γ is thus essential for pre-TCR function.