NK cell activation and CD4[sup]+[/sup] T cell α4β7 expression are associated with susceptibility to HIV-1

• Published in: The Journal of clinical investigation Vol. 135; no. 15; pp. 0_1 - 11
• Main Authors: Machmach, Kawthar, N'suessan, Kombo F, Farmer, Rohit, Godbole, Sucheta, Kim, Dohoon, McCormick, Lauren, Lima, Noemia S, Henry, Amy R, Laboune, Farida, Swafford, Isabella, Mika, Sydney K, Slike, Bonnie M, Currier, Jeffrey В, Eller, Leigh Anne, Ake, Julie A, Vasan, Sandhya, Robb, Merlin L, Krebs, Shelly J, Douek, Daniel C, Paquin-Proulx, Dominic
• Format: Journal Article
• Language: English
• Published: Ann Arbor American Society for Clinical Investigation 01.08.2025
• Subjects: CD4 antigen; Cell activation; Flow cytometry; Genotype & phenotype; HIV; Human immunodeficiency virus; Immunological memory; Infections; Lymphocytes; Lymphocytes T; Memory cells; Natural killer cells; Opsonization; Phenotypes; Regression analysis; Vaccines; Thailand
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/)C1195258

We leveraged specimens from the RV217 prospective study that enrolled participants at high risk of HIV-1 acquisition to investigate how NK cells, conventional T cells, and unconventional T cells influence HIV-1 acquisition. We observed low levels of a4B7 expression on memory CD4· T cells and invariant NK T (iNKT) cells, 2 cell types highly susceptible to HIV-1 infection, in highly exposed seronegative (HESN) compared with highly exposed seroconverter (HESC) participants. NK cells from HESN individuals had higher levels of a4p7 than did those from HESC individuals, presented a quiescent phenotype, and had a higher capacity to respond to opsonized target cells. We also measured translocated microbial products in plasma and found differences in phylum distribution between HESN and HESC participants that were associated with the immune phenotypes affecting the risk of HIV-1 acquisition. Finally, a logistic regression model combining features of NK cell activation, a4B7 expression on memory СО4· T cells, and T-box expressed in T cells (Tbet) expression by iNKT cells achieved the highest accuracy in identifying HESN and HESC participants. This immune signature, consisting of increased 467 on cells susceptible to HIV infection combined with higher NK cell activation and lower gut-homing potential, could affect the efficacy of HIV-1 prevention strategies such as vaccines.