CD8+ T Cells Prevent Lethality from Neonatal Murine Roseolovirus Infection [INFECTIOUS DISEASE AND HOST RESPONSE]

A recently described mouse homolog of the human roseoloviruses, murine roseolovirus (MRV), causes loss of peripheral and thymic CD4⁺ cells during neonatal infection of BALB/c mice. Despite significant disruptions to the normal adaptive immune response, infected BALB/c mice reproducibly recover from infection, consistent with prior studies on a related virus, mouse thymic virus. In this article, we show that, in contrast to published studies on mouse thymic virus, MRV appears to robustly infect neonatal C57BL/6 (B6) mice, causing severe depletion of thymocytes and peripheral T cells. Moreover, B6 mice recovered from infection. We investigated the mechanism of thymocyte and T cell loss, determining that the major thymocyte subsets were infected with MRV; however, CD4⁺ and CD4⁺CD8^– T cells showed increased apoptosis during infection. We found that CD8⁺ T cells populated MRV-infected thymi. These CD8⁺ T cells expressed markers of activation, had restricted TCR repertoire, and accumulated intracellular effector proteins, consistent with a cytotoxic lymphocyte phenotype and suggesting their involvement in viral clearance. Indeed, absence of CD8⁺ T cells prevented recovery from MRV infection and led to lethality in infected animals, whereas B cell–deficient mice showed CD4⁺ T cell loss but recovered from infection without lethality. Thus, these results demonstrate that CD8⁺ T cells are required for protective immunity against a naturally occurring murine pathogen that infects the thymus and establish a novel infection model for MRV in B6 mice, providing the foundation for detailed future studies on MRV with the availability of innumerable mutant mice on the B6 background.

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