Background

AUTHOR=Zaunders John , Danta Mark , Bailey Michelle , Mak Gerald , Marks Katherine , Seddiki Nabila , Xu Yin , Templeton David J. , Cooper David A. , Boyd Mark A. , Kelleher Anthony D. , Koelsch Kersten K. TITLE=CD4+ T Follicular Helper and IgA+ B Cell Numbers in Gut Biopsies from HIV-Infected Subjects on Antiretroviral Therapy Are Similar to HIV-Uninfected Individuals JOURNAL=Frontiers in Immunology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00438 DOI=10.3389/fimmu.2016.00438 ISSN=1664-3224 ABSTRACT=Background

Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4⁺ T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4⁺ subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV⁺ subjects on suppressive ART compared to HIV-negative controls (HNC).

Methods

Twenty-three HIV⁺ subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM⁺ epithelial cells, were accurately enumerated by flow cytometry, using counting beads.

Results

No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4⁺ T cell count/10⁶ epithelial cells was 2.4-fold lower in HIV⁺ subjects versus HNC (19,679 versus 47,504 cells; p = 0.02). Similarly, median LC CD4⁺ T cell counts were reduced in HIV⁺ subjects (8,358 versus 18,577; p = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA⁺ B cell counts at either site between HIV⁺ subjects and HNC. Further analysis showed no difference in CD4⁺, Tfh, or IgA⁺ B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4⁺ T cells, including CCR5⁺ cells, CD127⁺ long-term memory cells, CD103⁺ tissue-resident cells, or CD161⁺ cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells.

Conclusion

While there were lower absolute CD4⁺ counts in the TI and LC in HIV⁺ subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA⁺ B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.