Low levels of SIV-specific CD8+ T cells in germinal centers characterizes acute SIV infection
Folkvord, Joy M
Kovacs, Katalin J
Wagstaff, Reece K
Rendahl, Aaron K
Rakasz, Eva G
Skinner, Pamela J
AffiliationUniv Arizona, Div Infect Dis
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationLi, S., Folkvord, J. M., Kovacs, K. J., Wagstaff, R. K., Mwakalundwa, G., Rendahl, A. K., ... & Skinner, P. J. (2019). Low levels of SIV-specific CD8+ T cells in germinal centers characterizes acute SIV infection. PLoS pathogens, 15(3), e1007311.
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AbstractCD8+ T cells play an important role in controlling of HIV and SIV infections. However, these cells are largely excluded from B cell follicles where HIV and SIV producing cells concentrate during chronic infection. It is not known, however, if antigen-specific CD8+ T cells are excluded gradually as pathogenesis progresses from early to chronic phase, or this phenomenon occurs from the beginning infection. In this study we determined that SIV-specific CD8+ T cells were largely excluded from follicles during early infection, we also found that within follicles, they were entirely absent in 60% of the germinal centers (GCs) examined. Furthermore, levels of SIV-specific CD8+ T cells in follicular but not extrafollicular areas significantly correlated inversely with levels of viral RNA+ cells. In addition, subsets of follicular SIV-specific CD8+ T cells were activated and proliferating and expressed the cytolytic protein perforin. These studies suggest that a paucity of SIV-specific CD8+ T cells in follicles and complete absence within GCs during early infection may set the stage for the establishment of persistent chronic infection. Author summary A paucity of SIV-specific CD8+ T cells in lymphoid follicles and complete absence within most follicular germinal centers during early infection may set the stage for the establishment of persistent chronic infection.
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VersionFinal published version
SponsorsPublic Health Service grant from the National Institutes of Health [R01AI096966]; Wisconsin National Primate Research Center [P51OD011106/P51RR000167]; Wisconsin National Primate Research Center Pathology and Scientific Protocol Implementation Units; NIH Tetramer Core Facility [HHSN272201300006C]; NIH Nonhuman Primate Reagent Resource [R24 RR016001]; National Institute of Allergy and Infectious Diseases [HHSN 2722000900037C]
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