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Published on Apr 1, 2016
Cytomegalovirus infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T-cells within healthy donors. We show that such cells comprise up to 24% of the CD4+ T-cell pool and display a highly differentiated effector memory phenotype. Microarray analysis revealed a unique pattern of gene expression associated with cytotoxic function, chemokine secretion and response to epinephrine. The majority of CMV-specific CD4+ T-cells express granzyme B and perforin and this increases further during aging. CX3CR1 is also highly expressed and would direct cells towards fractalkine on inflamed endothelium. 47% of CMV-specific CD4+ T cells express the inhibitory marker PD-1 but this expression decreases during aging. These findings reveal the enormous accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the CMV-associated inflammatory and vascular complications that are observed in older people.