TY - JOUR
T1 - CD8+ T cells prevent lethality from neonatal murine roseolovirus infection
AU - Patel, Swapneel J.
AU - Yokoyama, Wayne M.
N1 - Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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+CD82 T cells showed increased apoptosis during infection. We found that CD8+ T cells populated MRVinfected 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.
AB - 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+CD82 T cells showed increased apoptosis during infection. We found that CD8+ T cells populated MRVinfected 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.
UR - http://www.scopus.com/inward/record.url?scp=85031996956&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1700982
DO - 10.4049/jimmunol.1700982
M3 - Article
C2 - 28972091
AN - SCOPUS:85031996956
SN - 0022-1767
VL - 199
SP - 3212
EP - 3221
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -