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

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.