T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection

Int J Mol Sci. 2024 May 29;25(11):5937. doi: 10.3390/ijms25115937.

Abstract

Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of naïve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells.

Keywords: HIV control; T cell homeostasis; immunology; long-term elite controllers (LTECs).

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Cohort Studies
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • HIV Infections* / virology
  • HIV Long-Term Survivors
  • HIV-1 / immunology
  • Homeostasis*
  • Humans
  • Male
  • Middle Aged
  • Viral Load

Grants and funding

This project was funded in part by grants RD16/0025/0013, PI16/01769, PI19/01237, and PI19/00973 and integrated into the State Plan for Scientific and Technical Research and Innovation; it was co-funded by the ISCIII Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (ERDF). The HIV BioBank, integrated into the Spanish AIDS Research Network, is partially funded by the RD16/0025/0019 project as part of the Plan Nacional R+D+I and cofinanced by ISCIII Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (ERDF).