CD4⁺ but not CD8⁺ T cells are required for protection against severe guinea pig cytomegalovirus infections

by Tyler B. Rollman, Zachary W. Berkebile, Dustin M. Hicks, Jason S. Hatfield, Priyanka Chauhan, Marco Pravetoni, Mark R. Schleiss, Gregg N. Milligan, Terry K. Morgan, Craig J. Bierle

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of infectious disease related birth defects worldwide. How the immune response modulates the risk of intrauterine transmission of HCMV after maternal infection remains poorly understood. Maternal T cells likely play a critical role in preventing infection at the maternal-fetal interface and limiting spread across the placenta, but concerns exist that immune responses to infection may also cause placental dysfunction and adverse pregnancy outcomes. This study investigated the role of CD4⁺ and CD8⁺ T cells in a guinea pig model of primary cytomegalovirus infection. Monoclonal antibodies specific to guinea pig CD4 and CD8 were used to deplete T cells in non-pregnant and in pregnant guinea pigs after mid-gestation. CD4⁺ T cell depletion increased the severity of illness, caused significantly elevated viral loads, and increased the rate of congenital guinea pig cytomegalovirus (GPCMV) infection relative to animals treated with control antibody. CD8⁺ T cell depletion was comparably well tolerated and did not significantly affect the weight of infected guinea pigs or viral loads in their blood or tissue. However, significantly more viral genomes and transcripts were detected in the placenta and decidua of CD8⁺ T cell depleted dams post-infection. This study corroborates earlier findings made in nonhuman primates that maternal CD4⁺ T cells play a critical role in limiting the severity of primary CMV infection during pregnancy while also revealing that other innate and adaptive immune responses can compensate for an absent CD8⁺ T cell response in α-CD8-treated guinea pigs.