The Colocalization Potential of HIV-specific CD8+ and CD4+ T-cells is Mediated by Integrin β7 but Not CCR6 and Regulated by Retinoic Acid

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Apr 4

PMID 22470433

Citations 14

Authors

Vanessa Sue Wacleche

Nicolas Chomont

Annie Gosselin

Patricia Monteiro

Mathieu Goupil

Hassen Kared

Cecile Tremblay

Nicole Bernard

Mohamed-Rachid Boulassel

Jean-Pierre Routy

Petronela Ancuta

Affiliations

Soon will be listed here.

Abstract

CD4(+) T-cells from gut-associated lymphoid tissues (GALT) are major targets for HIV-1 infection. Recruitment of excess effector CD8(+) T-cells in the proximity of target cells is critical for the control of viral replication. Here, we investigated the colocalization potential of HIV-specific CD8(+) and CD4(+) T-cells into the GALT and explored the role of retinoic acid (RA) in regulating this process in a cohort of HIV-infected subjects with slow disease progression. The expression of the gut-homing molecules integrin β7, CCR6, and CXCR3 was identified as a "signature" for HIV-specific but not CMV-specific CD4(+) T-cells thus providing a new explanation for their enhanced permissiveness to infection in vivo. HIV-specific CD8(+) T-cells also expressed high levels of integrin β7 and CXCR3; however CCR6 was detected at superior levels on HIV-specific CD4(+) versus CD8(+) T-cells. All trans RA (ATRA) upregulated the expression of integrin β7 but not CCR6 on HIV-specific T-cells. Together, these results suggest that HIV-specific CD8(+) T-cells may colocalize in excess with CD4(+) T-cells into the GALT via integrin β7 and CXCR3, but not via CCR6. Considering our previous findings that CCR6(+)CD4(+) T-cells are major cellular targets for HIV-DNA integration in vivo, a limited ability of CD8(+) T-cells to migrate in the vicinity of CCR6(+)CD4(+) T-cells may facilitate HIV replication and dissemination at mucosal sites.

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References

Douek D, Brenchley J, Betts M, Ambrozak D, Hill B, Okamoto Y . HIV preferentially infects HIV-specific CD4+ T cells. Nature. 2002; 417(6884):95-8. DOI: 10.1038/417095a. View

Yue F, Merchant A, Kovacs C, Loutfy M, Persad D, Ostrowski M . Virus-specific interleukin-17-producing CD4+ T cells are detectable in early human immunodeficiency virus type 1 infection. J Virol. 2008; 82(13):6767-71. PMC: 2447083. DOI: 10.1128/JVI.02550-07. View

Reiss Y, Proudfoot A, Power C, Campbell J, Butcher E . CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin. J Exp Med. 2001; 194(10):1541-7. PMC: 2193675. DOI: 10.1084/jem.194.10.1541. View

Acosta-Rodriguez E, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A . Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007; 8(6):639-46. DOI: 10.1038/ni1467. View

Brenchley J, Price D, Schacker T, Asher T, Silvestri G, Rao S . Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006; 12(12):1365-71. DOI: 10.1038/nm1511. View

Raffatellu M, Santos R, Verhoeven D, George M, Wilson R, Winter S . Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008; 14(4):421-8. PMC: 2901863. DOI: 10.1038/nm1743. View

Migueles S, Connors M . Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA. 2010; 304(2):194-201. DOI: 10.1001/jama.2010.925. View

Cicala C, Martinelli E, McNally J, Goode D, Gopaul R, Hiatt J . 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. Proc Natl Acad Sci U S A. 2009; 106(49):20877-82. PMC: 2780317. DOI: 10.1073/pnas.0911796106. View

El Hed A, Khaitan A, Kozhaya L, Manel N, Daskalakis D, Borkowsky W . Susceptibility of human Th17 cells to human immunodeficiency virus and their perturbation during infection. J Infect Dis. 2010; 201(6):843-54. PMC: 2849315. DOI: 10.1086/651021. View

10.

Chomont N, DaFonseca S, Vandergeeten C, Ancuta P, Sekaly R . Maintenance of CD4+ T-cell memory and HIV persistence: keeping memory, keeping HIV. Curr Opin HIV AIDS. 2011; 6(1):30-6. DOI: 10.1097/COH.0b013e3283413775. View

11.

Migueles S, Osborne C, Royce C, Compton A, Joshi R, Weeks K . Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity. 2008; 29(6):1009-21. PMC: 2622434. DOI: 10.1016/j.immuni.2008.10.010. View

12.

Lackner A, Veazey R . Current concepts in AIDS pathogenesis: insights from the SIV/macaque model. Annu Rev Med. 2007; 58:461-76. DOI: 10.1146/annurev.med.58.082405.094316. View

13.

Rodrigo Mora J, von Andrian U . Retinoic acid: an educational "vitamin elixir" for gut-seeking T cells. Immunity. 2004; 21(4):458-60. DOI: 10.1016/j.immuni.2004.10.002. View

14.

Manicassamy S, Ravindran R, Deng J, Oluoch H, Denning T, Kasturi S . Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med. 2009; 15(4):401-9. PMC: 2768543. DOI: 10.1038/nm.1925. View

15.

Ancuta P, Monteiro P, Sekaly R . Th17 lineage commitment and HIV-1 pathogenesis. Curr Opin HIV AIDS. 2010; 5(2):158-65. DOI: 10.1097/COH.0b013e3283364733. View

16.

Brainard D, Tager A, Misdraji J, Frahm N, Lichterfeld M, Draenert R . Decreased CXCR3+ CD8 T cells in advanced human immunodeficiency virus infection suggest that a homing defect contributes to cytotoxic T-lymphocyte dysfunction. J Virol. 2007; 81(16):8439-50. PMC: 1951383. DOI: 10.1128/JVI.00199-07. View

17.

Hunt P, Brenchley J, Sinclair E, McCune J, Roland M, Page-Shafer K . Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis. 2008; 197(1):126-33. PMC: 3466592. DOI: 10.1086/524143. View

18.

Williams I . CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Ann N Y Acad Sci. 2006; 1072:52-61. DOI: 10.1196/annals.1326.036. View

19.

Sheth P, Chege D, Shin L, Huibner S, Yue F, Loutfy M . Immune reconstitution in the sigmoid colon after long-term HIV therapy. Mucosal Immunol. 2008; 1(5):382-8. DOI: 10.1038/mi.2008.23. View

20.

Woodland D, Kohlmeier J . Migration, maintenance and recall of memory T cells in peripheral tissues. Nat Rev Immunol. 2009; 9(3):153-61. DOI: 10.1038/nri2496. View