Follicular CD8+ T-cells (fCD8) in GALT are associated with lower HIV-1 reservoir in the terminal ileum after ART initiated during PHI John Thornhill Imperial.

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Volume 23, Issue 3, Pages (March 2015)

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Follicular CD8+ T-cells (fCD8) in GALT are associated with lower HIV-1 reservoir in the terminal ileum after ART initiated during PHI John Thornhill Imperial College London No disclosures to declare

Follicular CD8+ T-cells (fCD8) in GALT are associated with lower HIV-1 reservoir in the terminal ileum after ART initiated during PHI B cells follicles - site of potential ongoing viral replication during treated HIV infection1 Follicular cytotoxic CD8 T-cells (fCD8) have the ability to migrate to B cell follicles and may be important for HIV control2,3 We examine for the presence of fCD8 in GALT and the association with HIV DNA GC IHC Control Tonsil: Bcl-6: Brown; CD8: Red; GC: germinal centre Banga, R. et al. Nat. Med. (2016) Leong YA et al. Nat Immunol (2016) He, R et al Nature (2016)

Methods Controls: Individuals undergoing routine endoscopy Primary HIV infection Controls: Individuals undergoing routine endoscopy Initiated on ART within 3 months of PHI Underwent colonoscopy with concurrent sampling from terminal ileum, rectum & PBMC

Results – Clinical Characteristics Primary HIV infection (n=21) Controls (n=7) Sex Male Female 21 3 4 Age 35 (27-39) 60 (46-71) Days from EDI to ART 62 (54-102) - Months on ART at biopsy 34 (22-46) At PHI Diagnosis CD4 CD4/CD8 HIV viral load 475 (443-644) 0.5 (0.4-0.8) 5.5 (4.5-5.9)

fCD8 cells are present at higher frequency in HIV+ rectal tissue compared to controls Gated on Live Singlets, Epcam-CD3+CD8+ Non-fCD8 fCD8

fCD8 are stable over time in treated PHI

fCD8 in GALT have higher expression of Bcl-6, Granzyme B & Perforin

fCD8 in the terminal ileum were associated with lower HIV DNA Rectum

Conclusions Follicular CD8+ T-cells are present & persist in GALT on ART They exhibit greater cytotoxic potential than non-fCD8 T-cells These cells may have a role in limiting HIV reservoir in TI GALT, during treated PHI Poster: TUPDA0104

Acknowledgements Thank you to all HEATHER study participants Prof Sarah Fidler, Prof P Klenerman & Prof John Frater, Dr Jonno Hoare & Simon Peake, Endoscopy at St Marys The Frater Group Genevieve Martin, Jodi Meyerowitz Matt Pace, Chansavath Phetsouphanh Helen Brown, Nicola Robinson & Natalia Olejniczak Lucia Parolini Chris Willberg, Emily Adland Prof Kholoud Porter, Wolfgang Stohr & all the CHERUB collaborators Prod Rob Goldin, Carolina Herrera at Imperial College BHIVA & MRC for their funding