Short Communication: Metformin Reduces CD4 T Cell Exhaustion in HIV-Infected Adults on Suppressive Antiretroviral Therapy
| Autor: | Cecilia M. Shikuma, Lishomwa C. Ndhlovu, Nancy Hanks, Ivo N. SahBandar, Lindsay B Kohorn, Glen M. Chew, Louie Mar A Gangcuangco, Eun-young Park, Dominic C. Chow, Mariana Gerschenson, Scott A. Souza |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male viruses T cell T-Lymphocytes Immunology Programmed Cell Death 1 Receptor HIV Infections Pilot Projects Lymphocyte Activation Outcomes Research 03 medical and health sciences 0302 clinical medicine Virology Hiv infected Medicine Humans 030212 general & internal medicine Receptors Immunologic Receptor Hepatitis A Virus Cellular Receptor 2 Cd4 t cell business.industry Effector virus diseases Middle Aged Immune Checkpoint Proteins Antiretroviral therapy Immune checkpoint Metformin CD4 Lymphocyte Count 030104 developmental biology Infectious Diseases medicine.anatomical_structure Anti-Retroviral Agents Female business medicine.drug |
| Zdroj: | AIDS Res Hum Retroviruses |
| Popis: | Increased negative immune checkpoint receptors (NCR) on T cells are linked to T cell exhaustion, dysfunctional effector responses, and HIV viral persistence. Metformin, an oral hypoglycemic agent used for diabetes, may have previously unrecognized beneficial immunologic effects. Using cryopreserved blood from a 24-week pilot study involving 12 virally suppressed HIV-infected individuals randomized 1:1 to metformin versus observation (OBS), we assessed change in the frequencies of T cell activation (CD38(+)HLA-DR(+)) and NCR [programmed cell death protein 1 (PD1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and T cell mucin-domain containing-3 (TIM3)]. No differences in 24-week change were seen between arms in CD4 or CD8 T cells, in the CD4/CD8 ratio, or in activated (CD38(+)HLA-DR(+)) CD4 or CD8 T cells. However, metformin over 24 weeks led to decreases compared with OBS in single PD1(+) (percent decrease: −9.6% vs. 7.5%, p = .015), in dual PD1(+)TIGIT(+) (−15.0% vs. 10.4%, p = .002), and in triple PD1(+)TIGIT(+)TIM3(+) (−24.0% vs. 8.1%, p = .041) CD4 T cells. Metformin led to no changes in CD8 T cell NCR frequencies. Metformin decreases the frequency of PD1(+), PD1(+)TIGIT(+), and PD1(+)TIGIT(+)TIM3(+) expressing CD4 T cells. This may have relevance to HIV cure strategies and to efforts to mitigate the risk of chronic complications of HIV. |
| Databáze: | OpenAIRE |
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