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Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Mar 15; Vol. 196 (6), pp. 2711-22. Date of Electronic Publication: 2016 Feb 12. - Publication Year :
- 2016
-
Abstract
- HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.<br /> (Copyright © 2016 by The American Association of Immunologists, Inc.)
- Subjects :
- Asymptomatic Diseases
Cell Differentiation
Cells, Cultured
HIV Infections virology
Host Specificity
Humans
Palatine Tonsil pathology
Phenotype
Programmed Cell Death 1 Receptor metabolism
Receptors, CXCR5 metabolism
Superinfection
T-Lymphocytes, Helper-Inducer virology
Virus Replication
Germinal Center immunology
HIV Infections immunology
HIV-1 physiology
T-Lymphocytes, Helper-Inducer immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 196
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26873986
- Full Text :
- https://doi.org/10.4049/jimmunol.1502174