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 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.
Rentenaar
R J
RJ
Renal Transplant Unit, Department of Medicine, Academic Medical Center, 1100 DE Amsterdam, The Netherlands. R.J.tenberge@amc.uva.nl
Gamadia
L E
LE
van DerHoek
N
N
van Diepen
F N
FN
Boom
R
R
Weel
J F
JF
Wertheim-van Dillen
P M
PM
van Lier
R A
RA
ten Berge
I J
IJ
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular; D016030:Kidney Transplantation / Q000009:adverse effects; D008137:Longitudinal Studies; D014019:Tissue Donors
D004279:DNA, Viral