Human cytomegalovirus-specific cytotoxic T cells: their precursor frequency and stage specificity

Abstract

Human virus‐specific cytotoxic T (T_c) cells may be important in maintaining the virus/host equilibrium during persistent herpes virus infections such as that with human cytomegalovirus (HCMV). We have previously shown that HCMV‐specific T_c cells are present in peripheral blood in normal asymptomatic seropositive individuals (L. K. Borysiewicz et al., Eur. J. lmrnunol. 1983. 13: 804). In this study we have used limiting dilution analysis to estimate the precursor frequency of these T_c cells and to further delineate their specificity for viral proteins expressed at different stages of the virus replicative cycle. HCMV‐specific T_c precursor cells were present in peripheral blood lymphocytes (PBL) at a frequency of 1/5000 to 20000 E⁺ PBL. This frequency was higher than that observed for varicella‐zoster virus (VZV)s‐pecific T_c cells (1/30000 to > 500 000) in asymptomatic individuals and was similar to the VZV T_c precursor cell frequencies observed following clinical reactivation (l/30000). When the stage specificity of clonally derived HCMV‐specific T_c cells was analyzed, using target cells treated with phosphonoformate to allow expression of only the nonstructural viral proteins, the majority (60%) of T_c cells lysed these cells. A number of T_c cells lysed only cells which expressed the structural or late HCMV proteins. These results suggest a high precursor frequency of HCMV‐specific T_c cells in PBL, and that there are subpopulations of such T_c cells specific for HCMV antigens expressed at different stages of the virus replicative cycle. However, the relative frequencies of these subpopulations suggest that the immunodominant HCMV antigens with respect to the T_c response are expressed at immediate early and/or early times.