In:
Journal of Virology, American Society for Microbiology, Vol. 85, No. 13 ( 2011-07), p. 6702-6713
Abstract:
Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8 + and CD4 + T cells but diminished rapidly in CD8 + T cells as the virus was controlled. Overall, the majority of IL-10-producing CD8 + T cells were specific for the immunodominant major histocompatibility complex (MHC) class I epitope. Unlike CD8 + T cells, a large proportion of CD4 + T cells within the CNS retained IL-10 production throughout persistence. Furthermore, elevated frequencies of IL-10-producing CD4 + T cells in the spinal cord supported preferential maintenance of IL-10 production at the site of viral persistence and tissue damage. IL-10 was produced primarily by the CD25 + CD4 + T cell subset during acute infection but prevailed in CD25 − CD4 + T cells during the transition to persistent infection and thereafter. Overall, these data demonstrate significant fluidity in the T-cell-mediated IL-10 response during viral encephalitis and persistence. While IL-10 production by CD8 + T cells was limited primarily to the time of acute effector function, CD4 + T cells continued to produce IL-10 throughout infection. Moreover, a shift from predominant IL-10 production by CD25 + CD4 + T cells to CD25 − CD4 + T cells suggests that a transition to nonclassical regulatory T cells precedes and is retained during CNS viral persistence.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.00200-11
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2011
detail.hit.zdb_id:
1495529-5
