The role of CD8+, CD57+ cells in human cytomegalovirus and other viral infections.

Peripheral blood lymphocytes expressing CD8 and CD57 determinants are a small (1-15%) subset in healthy humans. CD8+, CD57+ peripheral blood lymphocytes may be divided by the level of CD8 expression, into CD8+high (CD57+) T-cells and CD8+low (CD57+) natural killer (NK) cells. CD8+high (CD57+) T-cell numbers are increased in human cytomegalovirus (HCMV)-seropositive subjects, and there is substantial evidence that HCMV is integral in the development of this subset in health and disease. Furthermore, the CD8+high (CD57+) subset is clonally derived, expressing a limited range of T-cell receptors, and are therefore likely to have restricted antigen specificity. Functionally, CD8+low(CD57+) cells exhibit NK activity, while CD8+high(CD57+) T-cells from healthy subjects mediate contact-dependent suppression in several in vitro systems including: (i) pokeweed mitogen-induced proliferation and immunoglobulin synthesis, and (ii) generation of antiviral MHC-restricted cytotoxic T-lymphocytes. This is distinct from the nonspecific, soluble factor-mediated suppression exhibited from a phenotypically similar subset in human immunodeficiency virus (HIV) and bone marrow transplant recipients. This suggests an important immunoregulatory, suppressive role for CD8+high(CD57+) T-cells that may be potentiated by HCMV and altered in diseases associated with higher numbers of this subset including HIV, allograft recipients and rheumatoid arthritis.