DIFFERENTIAL EXPRESSION OF CD8-ALPHA AND CD8-BETA ASSOCIATED WITH MHC-RESTRICTED AND NON-MHC-RESTRICTED CYTOLYTIC EFFECTOR-CELLS

The differential expression of the α and β chains of the CD8 glycoprotein was examined in three functionally distinct cytolytic effector cell populations: (i) T cells (CD3+ CD56-), (ii) NK cells (CD56+ CD3-), and (iii) non-MHC-restricted T cells (CD56+ CD3+). Twenty-four percent of T cells were CD8+, and they consistently coexpressed both CD8α and CD8β. Moreover, CD8+ T cells uniformly expressed high-density CDSα. Forty percent of NK cells were CD8+ but the vast majority (~75%) expressed only CD8α without CD8β. In addition, CD8+ NK cells uniformly expressed low-density CD8α. In comparison, 75% of non-MHC-restricted T lymphocytes were CD8+ but they displayed an intermediate phenotype: 60% coexpressed CD8α and CD8β while 40% expressed only CD8α. Within this population, CD8α was expressed at high density, similar to that of T cells. Following IL-2 activation, enhancement of non-MHC-restricted cytotoxicity was not associated with any changes in either the quantitative or qualitative pattern of expression of CD8α or CD8β by these cells. Addition of either anti-CD8α or anti-CD8β mAb did not alter non-MHC-restricted cytotoxicity of either CD56+ CD3- or CD56+ CD3+ effector cells. However, within the CD56+ cell population, non-MHC-restricted cytotoxicity was almost entirely found within the CD8- and CD8α+β- populations, and both subsets displayed a similar level of killing. In contrast, CD8α+β+ cells exhibited very little non-MHC-restricted cytotoxicity. Thus, the coexpression of CD8α and CD8β in conjunction with the TCR/CD3 complex appears to characterize MHC restricted cells while the expression of CD8α alone is associated with non-MHC-restricted cytotoxicity. Taken together, these findings suggest that neither CD8α nor CD8β is involved in the initial phases of target cell binding or recognition during NK cell-mediated lysis. However, the selective expression of CD8α by a large fraction of non-MHC-restricted effector cells suggests that this antigen may play a different functional role in this unique subset of cytolytic lymphocytes. © 1990.