Human CD90 Identifies Th17/Tc17 T Cell Subsets That Are Depleted in HIV-Infected Patients

Abstract

By revisiting CD90, a GPI-anchored glycoprotein, we show that CD90 is expressed by a subset of CD4+ and CD8+ human T cells. CD4+CD90+ cells share similarities with Th17 cells because they express the Th17-specific transcription factor RORC2 and produce IL-17A. CD4+CD90+ cells are activated memory T cells that express the gut mucosal markers CCR6, CD161, and the α4 and β7 integrins. Compared with CD90-depleted CCR6+ memory Th17 cells, CD4+CD90+ cells express higher levels of IL-22 and proinflammatory cytokines (IL-6, TNF-α and GM-CSF), but they produce lower levels of IL-21 and no IL-9. Analyses of CD8+CD90+ cells reveal that they express RORC2 and are able to produce higher levels of IL-17A, IL-22, and CCL20 compared with CD90-depleted CD8+ cells. These data show that CD90 identifies Th17 and Tc17 cells with a peculiar cytokine profile. Studies of circulating CD90+ cells in HIV patients show that CD90+ cells are decreased with an imbalance of the CD4+CD90+/regulatory T cell ratio in nontreated patients compared with treated patients and healthy donors. Overall, human CD90 identifies a subset of Th17 and Tc17 cells within CD4+ and CD8+ T cells, respectively, which are depleted during HIV infection.

Increased Tryptophan Catabolism Is Associated With Increased Frequency of CD161+Tc17/MAIT Cells and Lower CD4+ T-Cell Count in HIV-1 Infected Patients on cART After 2 Years of Follow-Up

“…20 Importantly, combination antiretroviral therapy (cART) only partially restores the damaged mucosal barrier, and IL-17-producing CD4 + Th17 cells are depleted in HIV infection despite successful cART. 11,27,28 Also, CD8 + IL-17-producing cells, named Tc17 cells or mucosa-associated invariant T (MAIT) cells, have been suggested to play an important role in mucosal defense. In contrast to CD4 + Th17 cells, CD8 + Tc17/MAIT cells are considered to be a part of the innate immune system, important for mucosal integrity, and involved in the antibacterial and antifungal defense.…”

Preferential HIV Infection of CCR6 + Th17 Cells Is Associated with Higher Levels of Virus Receptor Expression and Lack of CCR5 Ligands

“…Lower frequencies of Th17 and Th1 cells were reported in the peripheral blood of aviremic HIV ϩ subjects on antiretroviral therapy (ART), but those of ART-naive patients were comparable with uninfected healthy subjects (9). More recently, depletion of CD4 Th17 with the CD90 marker and its imbalance relative to Treg was noted in untreated HIV-infected subjects compared to those in infected patients on ART and healthy controls (10). Partial to full recovery of Th17 responses was also observed in some patients on ART (11), although another study (12) found no difference in the frequencies of Th17 cells in the peripheral blood and colons from uninfected subjects, HIV ϩ subjects on ART, and HIV ϩ long-term nonprogressors.…”

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

“…In treatment-naive patients, some researchers established that peripheral T H 17 cells, contrary to the gastrointestinal tract, are not reduced [35,42,44], whereas others confirm a reduction in these cells [45][46][47]. Antiretroviral therapy (ART)-treated patients have lower peripheral blood T H 17 cells than untreated patients [35,44,48].…”