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

2000; American Society for Clinical Investigation; Volume: 105; Issue: 4 Linguagem: Inglês

10.1172/jci8229

1558-8238

Rob J. Rentenaar, Laila E. Gamadia, Nicolette van derHoek, Frank N.J. van Diepen, René Boom, Jan Weel, Pauline M. E. Wertheim‐van Dillen, René A. W. van Lier, Ineke J. M. ten Berge,

Immune Cell Function and Interaction

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 analyzed the kinetics and characteristics of cytomegalovirus-specific (CMV-specific) CD4(+) T cells in the course of primary CMV infection in kidney transplant recipients. Our data reveal that, as the first sign of specific immunity, circulating CMV-specific CD4(+) T cells become detectable with a median of 7 days after first appearance of CMV-DNA in peripheral blood. These cells produce the T helper 1 type (Th1) cytokines IFNgamma and TNFalpha, but 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 recovered from CMV infection earlier in life, virus-specific T cells do not cycle and express surface markers characteristic of memory T cells. After the initial rise, circulating virus-specific CD4(+) T cells decline rapidly. During this phase, a strong rise in IgM and IgG anti-CMV antibody titers occurs, concomitant with the reduction of CMV-DNA in the circulation.