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Mechanisms of T follicular helper (Tfh) impairment in chronic HIV infection
Journal article   Peer reviewed

Mechanisms of T follicular helper (Tfh) impairment in chronic HIV infection

Marita Chakhtoura, Rafael Cubas, Aarthi Talla, Virginie Tardif and Elias Haddad
The Journal of immunology (1950), v 198(1_Supplement), pp 214-214.13
01 May 2017
DOI: https://doi.org/10.4049/jimmunol.198.Supp.214.13

Abstract

Abstract Human immunodeficiency virus (HIV) infects millions of people worldwide. In secondary lymphoid organs, site where the anti-HIV immune response is mounted, the virus has been shown to induce a predominant dysregulation and disturbance of the microvenvironment. Previous work in our laboratory has identified the lack of protective anti-HIV antibodies in patients to be due, at least in part, to an inadequate T follicular helper (Tfh) cell help to germinal center (GC) B cells in draining lymph nodes through impaired PD-1/PD-L1 interactions. Since the mechanism of this impairment is not yet fully elucidated, we have used our co-culture assay followed by a unique gene array analysis to screen for key molecular pathways that could be accountable for the difference between helper programs in Tfh cells of HIV positive and negative individuals. The major driver of gene profile clustering was observed within Tfh proliferation programs as well as infection status. Gene set enrichment analysis included repair mechanisms, cell cycle regulation, metabolism, signal transduction and co-stimulation in the top 10 enriched pathways. Careful examination of gene fold changes in proliferating vs non-proliferating Tfh cells between healthy and HIV individuals showed a decrease with HIV, in immune regulatory gene expression such as the transcription factor c-maf and its mediators, responsible for Tfh differentiation, development, survival and performance. Investigating this pathway would contribute to a better understanding of the HIV-mediated dysregulation.

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