Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-α/β+ T cells and expansion of NK1.1+ TCR-γ/δ+ T cell development in CD3ζ-deficient mice

Abstract

The relationship between the structure of the T cell antigen receptor (TCR)-CD3 complex and development of NK1.1+ T cells was investigated. The TCR complex of freshly isolated NK1.1+ TCR-α/β+ thymocytes contained CD3ζ homodimers and CD3ζ-FcRγ heterodimers, whereas that of the majority of NK1.1- T cells did not contain FcRγ. The function of CD3ζ and FcRγ in the development of NK1.1+ T cells was determined by analyzing CD3ζ and FcRγ-deficient mice. The NK1.1+ T cells from wild-type and CD3ζ-deficient mice had equal levels of CD3 expression. However, the development of NK1.1+ TCR-α/β+ T cells was almost completely disrupted in thymus and spleen in CD3ζ-deficient mice, whereas no alteration was observed in FcRγ-deficient mice. In contrast, the number of novel NK1.1+ TCR-γ/β+ thymocytes expressing a surface phenotype similar to NK1.1+ TCR-α/β+ thymocytes increased approximately six times in CD3ζ-deficient mice. These findings establish the distinct roles of the CD3ζ chain in the development of the following different thymic T cell compartments: NK1.1+ TCR+, NK1.1+ TCR-α/β+, and NK1.1+ TCR-γ/δ+ thymocytes, which cannot be replaced by CD3η or FcRγ chains.