Analysis of the Proliferative T Cell Response to Human Cytomegalovirus Major Immediate‐Early Protein (IEl): Phenotype, Frequeney and Variability*

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Abstract
Cellular immune responses are important in the recovery from human cytomegalovirus (HCMV) infection. However, little is known about the CD4+T cell response and the target antigens (Ag) recognized. In this paper, we have analysed the proliferative T cell response of healthy HCMV seropositive (HCMV+) blood donors to recombinant immediate‐early proteins expressed in trans‐fected astrocytoma cells and to total HCMV Ags expressed in infected astrocytoma cells. We found that CD4+T cells were the major cell population that proliferated in the presence of IE or total HCMV Ags. Among healthy HCMV seropositive blood donors with anti‐HCMV specific proliferative response, 33–44% also responded to IE Ags. Moreover, in high responders, the precursor frequencies of cells which proliferated in the presence of total HCMV, IE, or IEl Ags were high (1/103 to 1/255, 1/2785 to 1/7744 and 1/5190 to 1/13531, respectively). In some donors, the anti‐IE response was variable over time, whereas the anti‐total HCMV Ags response remained constant, which suggests regulation of the anti‐IE response in immunocompetent subjects. Our results suggest that the CD4+anti‐IEl response represents a significant part of the anti‐HCMV proliferative response, both at the population level, and within individual immune systems.