Airway CD8+CD161++TCRvα7.2+ T Cell Depletion During Untreated HIV Infection Targets CD103 Expressing Cells

Abstract

HIV-infected adults are at an increased risk to lower respiratory tract infections (LRTIs). CD8 + CD161 ++ TCRvα7.2 + T cells are an innate-like T cell subset that are thought to play an important role in early defense against pathogens in the respiratory tract. HIV infection leads to irreversible depletion of these cells in peripheral blood, however, its impact on this subset in the human airway is still unclear. Here, we show presence of CD103 expressing CD8 + CD161 ++ TCRvα7.2 + T cells in the airway that exhibited a distinct cytokine functional profile compared to their CD103 − airway counterparts and those from peripheral blood. These CD103 expressing airway CD8 + CD161 ++ TCRvα7.2 + T cells were selectively depleted in untreated HIV-infected adults compared to healthy controls. Their frequency was positively correlated with frequency of airway CD4 + T cells. Furthermore, the frequency of airway CD8 + CD161 ++ TCRvα7.2 + T cells was also inversely correlated with HIV plasma viral load, while suppressive antiretroviral therapy (ART) resulted in restoration of airway CD8 + CD161 ++ TCRvα7.2 + T cells. Our findings show that CD103 expressing airway CD8 + CD161 ++ TCRvα7.2 + T cells are functionally distinct and are preferentially depleted during untreated asymptomatic HIV infection. Depletion of CD103 expressing airway CD8 + CD161 ++ TCRvα7.2 + T cells, at a major portal of pathogen entry, could partly contribute to the increased propensity for opportunistic LRTIs observed in untreated HIV-infected adults.

MR1-restricted MAIT cells from the human lung mucosal surface have distinct phenotypic, functional, and transcriptomic features that are preserved in HIV infection

“…Characterization of MAIT cell phenotype and function in HIV-positive individuals showed a decline in peripheral blood MAIT cells in HIV infection, as has been previously reported [16, 17], as well as a decline in MAIT cell frequency in the bronchoalveolar compartment. This finding is consistent with previous work that has reported a decline in lung mucosal MAIT cells in humans using the phenotypic definition of MAIT cells (CD8+CD161++TRAV1-2+), where MAIT cell frequency was reduced in a manner that was inversely correlated to viral load [18], as well as in the rhesus macaque model of SIV infection by MR1 tetramer definition [38]. We found that MAIT cell surface marker heterogeneity was preserved in bronchoalveolar MAIT cells in HIV infection, however, we did note a reduction in the frequency of CD161++CD26++ MAIT cells in both the bronchoalveolar and peripheral blood compartments.…”

“…In HIV infection, MAIT cells are depleted in peripheral blood and are functionally exhausted [16, 17]. The impact of HIV on MAIT cells at the lung’s mucosal surface is incompletely understood [18].…”

MR1-Restricted MAIT Cells From The Human Lung Mucosal Surface Have Distinct Phenotypic, Functional, and Transcriptomic Features That Are Preserved in HIV Infection

“…In HIV infection, MAIT cells are depleted in peripheral blood and are functionally exhausted ( 17 , 18 ). The impact of HIV on MAIT cells at the lung’s mucosal surface is incompletely understood ( 19 ).…”

MAIT Cells in Barrier Tissues: Lessons from Immediate Neighbors

“…In humans however, it is unclear to what extent tissue MAIT cells are permanently resident. Expression of aE-integrin (CD103) associated with CD8 + T RM cells is rare in blood MAIT cells (<3%) and common, but not universal, among MAIT cells within the oral and gastric mucosa (13,15), skin (31,57), and lungs (27)(28)(29) (Table 1). Thus tissues in health may represent a mixture of resident and recirculating MAIT cells, which could vary micro-anatomically: although most epidermal MAIT cells express CD103 and CLA (cutaneous lymphocyte antigen), only half of dermal MAIT cells express CD103 (31).…”

“…Thus tissues in health may represent a mixture of resident and recirculating MAIT cells, which could vary micro-anatomically: although most epidermal MAIT cells express CD103 and CLA (cutaneous lymphocyte antigen), only half of dermal MAIT cells express CD103 (31). Resident populations may behave differentially in diseasefor example, among bronchoalveolar CD8 + CD161 + + Va7.2 + cells, which are mostly MAIT cells, only the CD103+ fraction is depleted in HIV infection (28).…”