CONSTITUTIVE CD8 EXPRESSION ALLOWS INEFFICIENT MATURATION OF CD4-CELLS IN CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX MUTANT MICE( HELPER T)

Although mature CD4(+) T cells bear T cell receptors (TCRs) that recog nize class II major histocompatibility complex (MHC) and mature CD8(+) T cells bear TCRs that recognize class I MHC, it is possible that the initial commitment of an immature thymocyte to a CD4 or CD8 lineage i s made without regard to the specificity of the TCR. According to this model, CD4(+) cells with class I TCR do not mature because the CD8 co receptor is required for class I MHC recognition and positive selectio n. If this model is correct, constitutive expression of CD8 should all ow CD4(+) T cells with class I-specific TCRs to develop. In this repor t, we show that mature peripheral CD4(+) cells are present in class II MHC-deficient mice that express a constitutive CD8.1 transgene. These cells share a number of properties with the major class II MHC-select ed CD4 population, including the ability to express CD40 ligand upon a ctivation. Although mature CD4 cells are also detectable in the thymus of class II MHC mutant/CD8.1 transgenic mice, they represent a small fraction of the mature CD4 cells found in mice that express class II M HC. These results indicate that some T cells choose the CD4 helper lin eage independent of their antigen receptor specificity; however, the i nefficiency of generating class I-specific CD4 cells leaves open the p ossibility that an instructive signal generated upon MHC recognition m ay bias lineage commitment.