Discordant cellular and humoral immune responses to cytomegalovirus infection in healthy blood donors: Existence of a T_h 1-type dominant response

Previous studies have documented discordant cellular and humoral immune responses to subjects exposed to HIV-1, and that the nature of such responses may determine susceptibility and resistance to disease. We determined whether there is a spectrum of cellular versus humoral immunodominant responses to cytomegalovirus (CMV) infection. Blood samples from 50 healthy blood donors were tested for anti-CMV IgG antibodies and for proliferative responses of peripheral blood mononuclear cells (PBMC) to CMV antigens. Four patterns of immune responses to CMV were found: no detectable response (30%, Ab^-/Tc^-), anti-CMV IgG only (28%, Ab⁺/Tc^-), both anti-CMV IgG and T lymphocyte proliferation to CMV antigens (18%, Ab⁺/Tc⁺), and, interestingly, T lymphocyte proliferation to CMV only (24%, Ab^-/Tc⁺). To determine whether these immunodominant phenotypes correlate with the ability of PBMC to secrete IL-2 and IFN-γ in response to CMV antigens, we found that a greater percentage of individuals with a T cell proliferative response to CMV antigens (Ab^-/Tc⁺ and Ab⁺/Tc⁺) responded with increased IL-2 (P = 0.001) and IFN-γ levels (P = 0.002), compared to those without a proliferative response (Ab^-/Tc^- and Ab⁺/Tc^-). Our data therefore demonstrate that different individuals exhibit different immunodominant patterns of response to CMV. In particular, some individuals who are exposed to CMV fail to develop an antibody response but do develop cellular immunity. Whether these different patterns predict susceptibility or resistance to CMV-induced disease remains to be determined.