CD8 is either an alpha alpha homodimer or an alpha beta heterodimer, although most peripheral CD8-lineage T cells express only the CD8 alpha beta heterodimer. The physiological function of CD8 beta was elucidated with mice that were chimeric for the homozygous disruption of the CD8 beta gene. The CD8 betaminus / minus T cells developed normally to CD4plus CD8plus stage, but did not efficiently differentiate further, which resulted in few peripheral CD8plus T cells. The number of peripheral CD8plus T cells was restored by transfer of an exogenous CD8 beta gene into CD8 beta-deficient T cells. Thus, CD8 beta is necessary for the maturation of CD8plus T cells.