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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-08-2502.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2686-2692
IMMUNOBIOLOGY
Primary immune responses to human CMV: a critical role for
IFN- -producing CD4+ T cells in protection against CMV
disease
Laila E. Gamadia,
Ester B. M. Remmerswaal,
Jan F. Weel,
Frederieke Bemelman,
René A. W. van
Lier, and
Ineke J. M. Ten
Berge
From the Renal Transplant Unit, Department of Internal
Medicine, Laboratory for Experimental Immunology, Department of
Virology, and Division of Clinical Immunology and Rheumatology,
Academic Medical Center, Amsterdam, The Netherlands.
The correlates of protective immunity to disease-inducing
viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)-specific
CD4+ and CD8+ T cells in the course of primary
CMV infection in asymptomatic and symptomatic recipients of renal
transplants. Specific CD8+ cytotoxic T lymphocyte
(CTL) and antibody responses developed regardless of clinical signs.
CD45RA CD27+CCR7 CTLs,
although classified as immature effector cells in HIV
infection, were the predominant CD8 effector population in the acute
phase of protective immune reactions to CMV and were functionally
competent. Whereas in asymptomatic individuals the CMV-specific
CD4+ T-cell response preceded CMV-specific CD8+
T-cell responses, in symptomatic individuals the CMV-specific effector-memory CD4+ T-cell response was delayed and only
detectable after antiviral therapy. The appearance of disease symptoms
in these patients suggests that functional CD8+ T-cell and
antibody responses are insufficient to control viral replication and
that formation of effector-memory CD4+ T cells is necessary
for recovery of infection.
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