The influence of HIV infection on the balance of peripheral gut-homing Tc1/Treg and Tc17/Treg

Abstract

Abstract: Objective To investigate the influence of HIV infection on the balance of peripheral gut-homing CD8+T cell Tc1/Treg and Tc17/Treg. Methods 62 asymptomatic HIV infected patients as well as 41 healthy volunteers were recruited in this study. The patients were divided into two groups, which were the untreated and the treated group. The whole blood surface and intracellular cytokine staining were detected by BD FACSCanto, after that, the expression of gut-homing CD8+T cell subpopulation Tc1, Tc17 and Treg were analyzed by FACSDiva software and compared the differences of Tc1/Treg and Tc17/Treg ratio among different groups and the correlation with CD4 count and viral load. Results The ratio of peripheral gut homing Tc1/Treg increased significantly after HIV infection (24.68+16.12 vs 11.57±4.75,P<0.001), ART treatment can bring the ratio to the nearly normal level（15.43+13.90 vs 11.57±4.75,P=0.617）. Meanwhile, the ratio of peripheral gut homing Tc17/Treg showed a significant decrease（0.61±2.44 vs 1.02±0.95,P<0.001）. ART can not restore this ratio to normal (0.57±0.78 vs 0.61±2.44, P<0.001),which was still much lower than healthy control（0.57±0.78 vs 1.02±0.95,P<0.001）.The correlation analysis showed that the ratio of peripheral gut-homing Tc1/Treg was negatively correlated with viral load（r=-0.633,P<0.001）, but no relationship with CD4 count was found. Different to Tc1/Treg, the ratio of gut-homing Tc17/Treg were negatively correlated with viral load （r=-0.387,P=0.034）and positively with CD4 count（r=0.404,P=0.027）. Conclusion The peripheral gut-homing T cell functional subpopulation Tc1, Tc17 and Treg break homeostasis in vivo after HIV infection, which is correlated with disease progression. Antiretroviral therapy can not reconstitute this imbalances completely.

Key words: HIV, Gut-homing T cell, Tc1, Tc17, Treg

PENG Qiao-li, CHEN Lin, TANG Xian, JIANG Qiang, XIAO Jin-feng, HE Yun, WANG Hui. The influence of HIV infection on the balance of peripheral gut-homing Tc1/Treg and Tc17/Treg[J]. Electronic Journal of Emerging Infectious Diseases, 2017, 2(2): 76-80.

References

[1] Brenchley JM,Schacker TW,Ruff LE,et al.CD4+T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract[J].J Exp Med,2004,200(6):749-759.
[2] Arthos J,Cicala C,Martinelli E,et al.HIV-1 envelope protein binds to and signals through integrin alpha4beta7,the gut mucosal homing receptor for peripheral T cells[J].Nat Immunol,2008,9(3):301-309.
[3] Cicala C,Martinelli E,McNally JP,et al.The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1[J].Proc Natl Acad Sci U S A,2009, 106(49):20877-20882.
[4] Wang X,Xu H,Gill AF,et al.Monitoring alpha4beta7 integrin expression on circulating CD4+T cells as a surrogate marker for tracking intestinal CD4+T-cell loss in SIV infection[J].Mucosal Immunol,2009,2(6):518-526.
[5] Lu X,Li Z,Li Q,et al.Preferential loss of gut-homing α4β7 CD4+T cells and their circulating functional subsets in acute HIV-1 infection[J].Cell Mol Immunol. 2016,13(6):776-784.
[6] Peng Q,Wang H,Wang H,et al.Imbalances of guthoming CD4+ T-cell subsets in HIV-1-infected Chinese patients[J].J Acquir Immune Defic Syndr,2013,64(1):25-31.
[7] 彭巧丽,唐娴,蔡侃儒,等.HIV感染后外周血肠道归巢CD8细胞及其亚群变化特点研究[J].中国艾滋病性病,2017,23(4):274-279.
[8] Vukmanovic-Stejic M,Vyas B,Gorak-Stolinska P,et al.Human Tc1 and Tc2/Tc0 CD8 T-cell clones display distinct cell surface and functional phenotypes[J].Blood,2000, 95(1):231-240.
[9] Yen H R,Harris T J,S.Wada J F,et al.Tc17 CD8 T cells: functional plasticity and subset diversity[J].J Immunol, 2009,183(183):7161-7168.
[10] Le BL,Martin E,Peguillet I,et al.Antimicrobial activity of mucosal associated invariant T cells[J].Nat Immunol, 2010,11(8):701-708.
[11] Cecchinato V,Trindade CJ,Laurence A,et al.Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques[J].Mucosal Immunol,2008,1(4):279-288.
[12] Favre D,Lederer S,Kanwar B,et al.Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection[J].PLoS Pathog,2009,5(2):e1000295.
[13] Nigam P,Kwa S,Velu V,et al.Loss of IL-17-producing CD8T cells during late chronic stage of pathogenic SIV infection[J].J Immunol,2011,186(2):745-753.
[14] Cosgrove C,Ussher JE,Rauch A,et al.Early and nonreversible decrease of CD161++/MAIT cells in HIV infection[J].Blood,2013,21(6):951-961.
[15] Klatt NR,Estes JD,Sun X,et al.Loss of mucosal CD103+DCs and IL-17+ and IL-22+lymphocytes is associated with mucosal damage in SIV infection[J].Mucosal Immunol, 2012,5(6):646-657.
[16] Favre D,Mold J,Hunt PW,et al.Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease[J].Sci Tra Med, 2010,19(2):32-36.
[17] Jenabian MA,El-Far M,Vyboh K,et al.Immunosuppressive Tryptophan Catabolism and Gut Mucosal Dysfunction Following Early HIV Infection[J].J Infect Dis,2015, 212(3):355-366.