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

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 α4β7 expression on memory CD4+ T cells and invaria...

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Published inThe Journal of clinical investigation Vol. 135; no. 15
Main Authors Machmach, Kawthar, N’guessan, 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 R., Eller, Leigh Anne, Ake, Julie A., Vasan, Sandhya, Robb, Merlin L., Krebs, Shelly J., Douek, Daniel C., Paquin-Proulx, Dominic
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 01.08.2025
Subjects
Adult
CD4-Positive T-Lymphocytes - immunology
Disease Susceptibility
Female
HIV Infections - immunology
HIV-1 - immunology
Humans
Integrins
Killer Cells, Natural - immunology
Killer Cells, Natural - pathology
Lymphocyte Activation - immunology
Male
Middle Aged
Natural Killer T-Cells - immunology
Natural Killer T-Cells - pathology
Prospective Studies
Infectious disease
AIDS/HIV
NK cells
NKT cells
T cells
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Abstract 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 α4β7 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 α4β7 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, α4β7 expression on memory CD4+ 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 α4β7 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.
AbstractList 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 α4β7 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 α4β7 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, α4β7 expression on memory CD4 + 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 α4β7 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. We propose a model whereby increased α4β7 expression on cells susceptible to HIV infection combined with higher NK cell activation and lower gut-homing potential is associated with an increased risk of HIV acquisition.
We leveraged specimens from the RV217 prospective study that enrolled participants at high risk of HIV-1 acquisition to investigate how NK, conventional T cells, and unconventional T cells influence HIV-1 acquisition. We observed low levels of α4β7 expression on memory CD4 T cells and iNKT cells, two cell types highly susceptible to HIV-1 infection, in highly exposed seronegative (HESN) compared to highly exposed seroconverter (HESC) participants. NK cells from HESN had higher levels of α4β7 compared to HESC, 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 that were associated with the immune phenotypes impacting the risk of HIV-1 acquisition. Finally, a logistic regression model combining features of NK cells activation, α4β7 expression on memory CD4 T cells, and Tbet expression by iNKT cells achieved the highest accuracy in identifying HESN and HESC participants. This immune signature comprised of increased α4β7 on cells susceptible to HIV infection combined with higher NK cells activation and lower gut homing potential could impact the efficacy of HIV-1 prevention strategies such as vaccines.We leveraged specimens from the RV217 prospective study that enrolled participants at high risk of HIV-1 acquisition to investigate how NK, conventional T cells, and unconventional T cells influence HIV-1 acquisition. We observed low levels of α4β7 expression on memory CD4 T cells and iNKT cells, two cell types highly susceptible to HIV-1 infection, in highly exposed seronegative (HESN) compared to highly exposed seroconverter (HESC) participants. NK cells from HESN had higher levels of α4β7 compared to HESC, 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 that were associated with the immune phenotypes impacting the risk of HIV-1 acquisition. Finally, a logistic regression model combining features of NK cells activation, α4β7 expression on memory CD4 T cells, and Tbet expression by iNKT cells achieved the highest accuracy in identifying HESN and HESC participants. This immune signature comprised of increased α4β7 on cells susceptible to HIV infection combined with higher NK cells activation and lower gut homing potential could impact the efficacy of HIV-1 prevention strategies such as vaccines.
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 α4β7 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 α4β7 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, α4β7 expression on memory CD4+ 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 α4β7 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.
Author Kim, Dohoon
Krebs, Shelly J.
Douek, Daniel C.
Ake, Julie A.
Godbole, Sucheta
Lima, Noemia S.
Swafford, Isabella
Henry, Amy R.
Laboune, Farida
Paquin-Proulx, Dominic
Mika, Sydney K.
Robb, Merlin L.
Slike, Bonnie M.
Farmer, Rohit
Machmach, Kawthar
McCormick, Lauren
Currier, Jeffrey R.
Vasan, Sandhya
Eller, Leigh Anne
N’guessan, Kombo F.
AuthorAffiliation 2 Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, Maryland, USA
4 Viral Diseases Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
3 Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA
1 US Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
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Keywords Infectious disease
AIDS/HIV
NK cells
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T cells
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Snippet We leveraged specimens from the RV217 prospective study that enrolled participants at high risk of HIV-1 acquisition to investigate how NK cells, conventional...
We leveraged specimens from the RV217 prospective study that enrolled participants at high risk of HIV-1 acquisition to investigate how NK, conventional T...
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SubjectTerms Adult
CD4-Positive T-Lymphocytes - immunology
Disease Susceptibility
Female
HIV Infections - immunology
HIV-1 - immunology
Humans
Integrins
Killer Cells, Natural - immunology
Killer Cells, Natural - pathology
Lymphocyte Activation - immunology
Male
Middle Aged
Natural Killer T-Cells - immunology
Natural Killer T-Cells - pathology
Prospective Studies
Title NK cell activation and CD4+ T cell α4β7 expression are associated with susceptibility to HIV-1
URI https://www.ncbi.nlm.nih.gov/pubmed/40338667
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https://pubmed.ncbi.nlm.nih.gov/PMC12321385
Volume 135
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