Development of virus-specific CD4(+) T cells during primary cytomegalovirus infection

Although virus-specific CD4(+) T cells have been characterized extensively in latently infected individuals, it is unclear how these protective T-cell responses develop during primary virus infection in humans. Here, we analy zed the kinetics and. characteristics of cytomegalovirus-specific (CMV-spec ific) CD4(+) T cells in the course of primary CMV infection in kidney trans plant recipients. Our data reveal that, as the first sign of specific immun ity, circulating CMV-specific CD4(+) T cells become detectable with a media n of 7 days after first appearance of CMV-DNA in peripheral blood. These ce lls produce the T helper 1 type (Th1) cytokines IFN gamma and TNF alpha, bu t not the T helper 2 type (Th2) cytokine IL4. In primary CMV infection, the vast majority of these circulating virus-specific T cells have features of recently activated naive T cells in that they coexpress CD45RA and CD45R0 and appear to be in the cell cycle. In contrast, in people who have recover ed from CMV infection earlier in life, virus-specific T cells do not cycle and express surface markers characteristic of memory T cells. After the ini tial rise, circulating virus specific CD4(+) T cells decline rapidly. Durin g this phase, a strong rise in IgM and IgG anti-CMV antibody titers occurs, concomitant with the reduction of CMV-DNA in the circulation.