Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections

Abstract

Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, GI tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2) Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the GI tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and GI tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys.

Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals

“…Preferential depletion of Th17 CD4 T cells has been found in HIV-infected individuals as well as in pathogenic SIV-infected monkeys (24). Our data showed that a significant fraction of Ad5-specific CD4 T cells, but not CMV-specific CD4 T cells, produce IL-17.…”

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…First and foremost, it is possible that a different "quality" of CD4 ϩ T-cell depletion in natural versus nonnatural SIV hosts at the intestinal mucosal level plays a major role. Indeed, both SIV-infected RM and HIV-infected persons experience a significant and preferential reduction of the IL-17-producing CD4 ϩ (Th17) and CD8 ϩ (Tc17) T-cell subsets throughout the gastrointestinal tract (81)(82)(83)(84). Similarly, the depletion of IL-17-producing innate lymphocytes in the GI tracts of SIV-infected Asian macaques has been demonstrated (85,86).…”

Immunovirological parameters and cytokines in HIV infection

“…The high susceptibility of Th17 cells to HIV, due to the large tropism of the virus in response to CCR5 chemokine receptor, is reflected in the depletion of this profile, in both the PBMC and gut-associated lymphoid tissue (GALT) of seropositive patients 88,89 . However, Th17 cells were found preserved in LTNP individuals 90 .…”