Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008;112(7):2826-35

Human Immunology Section, Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Blood (Impact Factor: 10.45). 08/2008; 112(7):2826-35. DOI: 10.1182/blood-2008-05-159301
Source: PubMed


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.

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    • "IL-17A is the signature cytokine of Th17 cells, the differentiation of which is controlled by nuclear transcription factor RORγt and determined by the availability of cytokines such as TGF-β and IL-6 in humans (Manel et al., 2008; Yang et al., 2008; Zhou et al., 2008). As has been well established that CD4+ T cells, including Th1, Th2, Tregs and Th17, were dramatically depleted soon after HIV-1 infection; and Th17 cells were preferentially depleted in the intestinal mucosa (Brenchley et al., 2008; Veazey et al., 1998). It has also been shown that IL-17A could affect the expression of TJ-associated genes (Kinugasa et al., 2000). "
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    ABSTRACT: Background Mucosal barrier dysfunction might play a key role in HIV/AIDS, yet the early effects of HIV-1 on intestinal mucosal barrier, especially tight junctions (TJ) have not been well addressed. Aims To investigate the effects of acute HIV-1 infection on the expression of intestinal IL-17A and TJ-associated genes using an NHP-AIDS model. Methods TaqMan probe real-time RT-PCR methods were established and claudin-1, claudin-3, occludin and zonula occluden-1 (ZO-1) mRNA levels in the duodenal biopsies of rhesus macaques collected before and after rectal exposures to SHIV-SF162P4 were examined and compared with that of IL-17A, IL-6, TGF-β, RORγt, T-bet, Foxp3 and GATA-3. Results The mRNA levels of TJ-associated genes were statistically significantly reduced soon after viral exposures and the mRNA levels of claudin-1, occludin and ZO-1 in viral positive tissues (from Group I) were lower than that in viral negative tissues (from Group II) after viral exposure. IL-17A mRNA levels were also decreased and positively correlated with the mRNA levels of the TJ-associated genes after viral exposure or infection, although the levels of IL-6, TGF-β and RORγt mRNA showed no statistical difference. The levels of GATA-3 mRNA in tissues collected before viral exposure were statistically different between Group I and Group II animals. The balance between T-bet and GATA-3 mRNA levels in Group II was markedly altered and statistically significantly different from that in Group I. Conclusions Acute SHIV, and by extension HIV infection could affect the expression of TJ-associated genes, probably through IL-17A and other immune alterations.
    Full-text · Article · Oct 2014 · Experimental and Molecular Pathology
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    • "Pathogenic lentivirus infection is associated with extensive depletion of the gut Th17 subset which plays a key role in bacterial defense [13,14,38-40], raising the possibility that the Th subsets in the LP may have different susceptibilities to HIV-1 mediated killing. We therefore investigated the susceptibility of Th1 (IFN-γ+IL-17-), Th17 (IL-17+IFN-γ-), Th1/17 (IFN-γ+ IL-17+) and non-Th1/17 (IFN-γ-IL-17-, double negative, DN) subsets to undergo HIV-1 mediated death at 6 dpi in the presence or absence of bacteria. "
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    • "The investigators have also identified a preferential loss of Th17 subsets from the GI tract51. Further studies comparing the pathogenic (pigtailed macaques) with the non pathogenic SIV models (African green monkey) revealed loss of Th17 cells with a concomitant increase in Treg752 in the pigtail macaques. "
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    ABSTRACT: HIV continues to be a major health problem worldwide even today. Owing to the intricate nature of its interactions with the immune system, HIV has remained an enigma that cleverly utilizes the host machinery to survive. Its ability to evade the host immune system, at both levels, innate and adaptive, allows the pathogen to replicate and transmit from one host to another. It has been shown that HIV has multipronged effects especially on the adaptive immunity, with CD4+ T cells being the worst affected T cell populations. Various analyses have revealed that the exposure to HIV results in clonal expansion and excessive activation of the immune system. Also, an abnormal process of differentiation has been observed suggestive of an alteration and blocks in the maturation of various T cell subsets. Additionally, HIV has shown to accelerate immunosenescence and exhaustion of the overtly activated T cells. Apart from causing phenotypic changes, HIV has adverse effects on the functional aspect of the immune system, with evidences implicating it in the loss of the capacity of T cells to secrete various antiviral cytokines and chemokines. However, there continues to be many aspects of the immunopathogenesis of HIV that are still unknown and thus require further research to convert the malaise of HIV into a manageable epidemic.
    No preview · Article · Nov 2013 · The Indian Journal of Medical Research
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