Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 203, Issue 13, Pages 2865-2877Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20052246
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Funding
- MRC [G108/441] Funding Source: UKRI
- Medical Research Council [G108/441] Funding Source: researchfish
- Intramural NIH HHS Funding Source: Medline
- Medical Research Council [G108/441] Funding Source: Medline
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The role of CD4(+) T cells in the control of persistent viral infections beyond the provision of cognate help remains unclear. We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1 beta, and surface mobilization of the degranulation marker CD107a by CD4(+) T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes. Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4(+) T cell maturation. The functional profile of virus-specific CD4(+) T cells in chronic CMV infection was unique compared with that observed in other viral infections. Salient features of this profile were: ( a) the simultaneous production of MIP-1 beta, TNF-alpha, and IFN-gamma in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes. This polyfunctional profile was associated with a terminally differentiated phenotype that was not characterized by a distinct clonotypic composition. Thus, mature CMV-specific CD4(+) T cells exhibit distinct functional properties reminiscent of antiviral CD8(+) T lymphocytes.
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