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/106epithelial 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.


CONCLUSIONS
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.
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.
John
J
Zaunders
St Vincent's Hospital, Clinical School , Sydney, NSW , Australia.
Mark
M
Danta
The Kirby Institute, The University of New South Wales , Sydney, NSW , Australia.
Michelle
M
Bailey
St Vincent's Hospital, Clinical School , Sydney, NSW , Australia.
Gerald
G
Mak
St Vincent's Centre for Applied Medical Research, St Vincent's Hospital , Sydney, NSW , Australia.
Katherine
K
Marks
Equipe 16, INSERM U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France.
Nabila
N
Seddiki
The Kirby Institute, The University of New South Wales , Sydney, NSW , Australia.
Yin
Y
Xu
The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia; RPA Sexual Health, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
David J
DJ
Templeton
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.
David A
DA
Cooper
The Kirby Institute, The University of New South Wales , Sydney, NSW , Australia.
Mark A
MA
Boyd
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.
Anthony D
AD
Kelleher
The Kirby Institute, The University of New South Wales , Sydney, NSW , Australia.
Kersten K
KK
Koelsch
CD4+ T lymphocytes; HIV; IgA B cells; T follicular helper cells; germinal centers; gut-associated lymphoid tissue