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Front Immunol. 2016 Oct 24;7:438. eCollection 2016.

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.

Author information

1
St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, NSW, Australia; The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.
2
St Vincent's Hospital, Clinical School , Sydney, NSW , Australia.
3
The Kirby Institute, The University of New South Wales , Sydney, NSW , Australia.
4
St Vincent's Centre for Applied Medical Research, St Vincent's Hospital , Sydney, NSW , Australia.
5
Equipe 16, INSERM U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France.
6
The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia; RPA Sexual Health, Royal Prince Alfred Hospital, Sydney, NSW, Australia.

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.

KEYWORDS:

CD4+ T lymphocytes; HIV; IgA B cells; T follicular helper cells; germinal centers; gut-associated lymphoid tissue

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