HIV-infected spleens present altered follicular helper T cell (Tfh) subsets and skewed B cell maturation

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Abstract

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.

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Colineau, L., Rouers, A., Yamamoto, T., Xu, Y., Urrutia, A., Pham, H. P., … Graff-Dubois, S. (2015). HIV-infected spleens present altered follicular helper T cell (Tfh) subsets and skewed B cell maturation. PLoS ONE, 10(10). https://doi.org/10.1371/journal.pone.0140978

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