CD1d-Independent Developmental Acquisition of Prompt IL-4 Gene Inducibility in Thymus CD161(NKl)-CD44~(low)CD4~+CD8~-T Cells Is Associated with Complementarity Determining Region 3-Diverse and Biased Vbeta2/Vbeta7/Vbeta8/Valpha3.2 T Cell Receptor Usa

摘要

Among Ag-inexperienced naive T cells,the CD1d-restricted NKT cell that uses invariant TCR-alpha-chain is the most widely studied cell capable of prompt IL-4 inducibility.We show in this study that thymus CD161~-CD44~(low)CD4~+CD8~-T cells promptly produce IL-4 upon TCR stimulation,a response that displays biased Vbeta(2/7/8)and Valpha3.2 TCR usage.The association of Vbeta family bias and IL-4 inducibility in thymus CD161~-CD44~(low)CD4~+CD8~-T cells is found for B6,B10,BALB/c,CBA,B10.A(4R),and ICR mouse strains.Despite reduced IL-4 inducibility,there is a similarly biased Vbeta(2/7/8)TCR usage by IL-4 inducibility~+ spleen CD161~-CD44~(low)CD4~+CD8~-T cells.Removal of alpha-galacotosylceramide/CD1d-binding cells from CD161~CD44~(low)CD4~+CD8~-thymocytes does not significantly affect their IL-4 inducibility.The development of thymus CD161~-CD44~(low)CD4~+CD8~-T cells endowed with IL-4 inducibility and their associated use of Vbeta(2/7/8)are beta_2-microglobulin-,CD1d-,and p59~(fyn)-independent.Thymus CD161~-CD44~(low)CD4~+CD8~-T cells produce low and no IFN-gamma inducibility in response to TCR stimulation and to IL-12 + IL-18,respectively,and they express diverse complementarity determining region 3 sequences for both TCR-alpha-and-beta-chains.Taken together,these results demonstrate the existence of a NKT cell distinct,TCR-repertoire diverse naive CD4~+ T cell subset capable of prompt IL-4 inducibility.This subset has the potential to participate in immune response to a relatively large number of Ags.The more prevalent nature of this unique T cell subset in the thymus than the periphery implies roles it might play in intrathymic T cell development and may provide a framework upon which mechanisms of developmentally regulated IL-4 gene inducibility can be studied.