| Title: |
HIV-infected spleens present altered follicular helper T cell (Tfh) subsets and skewed B cell maturation |
| Authors: |
Colineau, L; Rouers, A; Yamamoto, T; Xu, Y; Urrutia, A; Pham, HP; Cardinaud, S; Samri, A; Dorgham, K; Coulon, PG; Cheynier, R; Hosmalin, A; Oksenhendler, E; Six, A; Kelleher, AD; Zaunders, J; Koup, RA; Autran, B; Moris, A; Graff-Dubois, S |
| Contributors: |
Unutmaz, Derya |
| Source: |
urn:ISSN:1932-6203 ; Plos One, 10, 10, e0140978 |
| Publisher Information: |
Public Library of Science (PLoS) |
| Publication Year: |
2015 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
3207 Medical Microbiology; 32 Biomedical and Clinical Sciences; 3204 Immunology; Prevention; Infectious Diseases; Vaccine Related (AIDS); Genetics; Vaccine Related; Immunization; HIV/AIDS; 2.1 Biological and endogenous factors; Inflammatory and immune system; Infection; 3 Good Health and Well Being; B-Lymphocytes; Cell Differentiation; Cytokines; DNA; Viral; Flow Cytometry; Gene Expression Profiling; HIV Infections; Humans; Real-Time Polymerase Chain Reaction; STAT3 Transcription Factor; Spleen; T-Lymphocytes; Helper-Inducer; Virus Integration; anzsrc-for: 3207 Medical Microbiology |
| Description: |
Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV + ) individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined. Using a unique collection of splenocytes, we compared the frequency, phenotype and transcriptome of Tfh subsets in spleens from HIV negative (HIV - ) and HIV + subjects. We observed an increase of CXCR5 + PD-1 PD-1 high CD57 - Tfh and germinal center (GC) CD57+ Tfh in HIV + spleens. Both subsets showed a reduced mRNA expression of the transcription factor STAT-3, co-stimulatory, regulatory and signal transduction molecules as compared to HIV - spleens. Similarly, Foxp3 expressing follicular regulatory T (Tfr) cells were increased, suggesting sustained GC reactions in chronically HIV + spleens. As a consequence, GC B cell populations were expanded, however, complete maturation into memory B cells was reduced in HIV + spleens where we evidenced a compromised production of B cell-activating cytokines such as IL-4 and IL-10. Collectively our data indicate that, although Tfh proliferation and GC reactions seem to be ongoing in HIV-infected spleens, Tfh "differentiation" and expression of costimulatory molecules is skewed with a profound effect on B cell maturation. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
http://purl.org/au-research/grants/nhmrc/APP1052979; http://purl.org/au-research/grants/nhmrc/APP1020536; https://hdl.handle.net/1959.4/unsworks_38867; https://doi.org/10.1371/journal.pone.0140978 |
| DOI: |
10.1371/journal.pone.0140978 |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_38867; https://doi.org/10.1371/journal.pone.0140978 |
| Rights: |
metadata only access ; http://purl.org/coar/access_right/c_14cb ; CC-BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.82B15EBE |
| Database: |
BASE |