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 res ponses to subjects exposed to HIV-1, and that the nature of such responses may determine susceptibility and resistance to disease. We determined wheth er there is a spectrum of cellular versus humoral immunodominant responses to cytomegalovirus (CMV) infection. Blood samples from 50 healthy blood don ors were tested for anti-CMV IgG antibodies and for proliferative responses of peripheral blood mononuclear cells (PBMC) to CMV antigens, Four pattern s 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 lymphocy te proliferation to CMV antigens (18%, Ab(+)/Tc+), and, interestingly, T ly mphocyte proliferation to CMV only (24%, Ab(-)/Tc+). To determine whether t hese immunodominant phenotypes correlate with the ability of PBMC to secret e IL-2 and IFN-gamma in response to CMV antigens, we found that a greater p ercentage of individuals with a T cell proliferative response to CMV antige ns (Ab(-/)Tc(+) and Ab(+/)Tc(+)) responded with increased IL-2 (P = 0.001) and IFN-gamma levels (P = 0.002), compared to those without a proliferative response (Ab(-)/Tc- and Ab(+)/Tc-). Our data therefore demonstrate that di fferent individuals exhibit different immunodominant patterns of response t o CMV. In particular, some individuals who are exposed to CMV fail to devel op an antibody response but do develop cellular immunity. Whether these dif ferent patterns predict susceptibility or resistance to CMV-induced disease remains to be determined.