4.8 Article

Delayed antiretroviral therapy in HIV-infected individuals leads to irreversible depletion of skin- and mucosa-resident memory T cells

期刊

IMMUNITY
卷 54, 期 12, 页码 2842-+

出版社

CELL PRESS
DOI: 10.1016/j.immuni.2021.10.021

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资金

  1. Clinician Scientist Grant of the Austrian Society of Dermatology and Venereology [AP00871OFF]
  2. Medical Scientific Fund of the Mayor of the City of Vienna [18127]
  3. Oesterreichische Nationalbank (Austrian Central Bank) [17872]
  4. Oesterreichische Nationalbank (Anniversary Fund) [17872]
  5. Austrian Science Fund [P31494]
  6. Austrian Science Fund (FWF) [P31494] Funding Source: Austrian Science Fund (FWF)

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Research reveals an irreversible loss of CXCR3(+) Trm cells in the skin and mucosa of PLWH who received late ART treatment, which may be a precipitating factor in the development of HPV-related cancer.
People living with HIV (PLWH) are at increased risk for developing skin and mucosal malignancies despite systemic reconstitution of CD4(+) T cells upon antiretroviral therapy (ART). The underlying mechanism of chronic tissue-related immunodeficiency in HIV is unclear. We found that skin CD4(+) tissue-resident memory T (Trm) cells were depleted after HIV infection and replenished only upon early ART initiation. TCR clonal analysis following early ART suggested a systemic origin for reconstituting CD4(+) Trm cells. Single-cell RNA sequencing in PLWH that received late ART treatment revealed a loss of CXCR3(+) Trm cells and a tolerogenic skin immune environment. Human papilloma virus-induced precancerous lesion biopsies showed reduced CXCR3(+) Trm cell frequencies in the mucosa in PLWH versus HIV- individuals. These results reveal an irreversible loss of CXCR3(+) Trm cells confined to skin and mucosa in PLWH who received late ART treatment, which may be a precipitating factor in the development of HPV-related cancer.

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