Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection

Edwin Leeansyah, Anupama Ganesh, Máire F. Quigley, Anders Sönnerborg, Jan Andersson, Peter W. Hunt, Ma Somsouk, Steven G. Deeks, Jeffrey N. Martin, Markus Moll, Barbara Shacklett, Johan K. Sandberg

Research output: Contribution to journalArticle

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Abstract

Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved antimicrobial MR1-restricted T-cell subset. MAIT cells are CD161+, express a Vα7.2 TCR, are primarily CD8+ and numerous in blood and mucosal tissues. However, their role in HIV-1 infection is unknown. In this study, we found levels of MAIT cells to be severely reduced in circulation in patients with chronic HIV-1 infection. Residual MAIT cells were highly activated and functionally exhausted. Their decline was associated with time since diagnosis, activation levels, and the concomitant expansion of a subset of functionally impaired CD161- Vα7.2+ T cells. Such cells were generated in vitro by exposure of MAIT cells to Escherichia coli. Notably, whereas the function of residual MAIT cells was at least partly restored by effective antiretroviral therapy, levels of MAIT cells in peripheral blood were not restored. Interestingly, MAIT cells in rectal mucosa were relatively preserved, although some of the changes seen in blood were recapitulated in the mucosa. These findings are consistent with a model in which the MAIT-cell compartment, possibly as a result of persistent exposure to microbial material, is engaged, activated, exhausted, and progressively and persistently depleted during chronic HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)1124-1135
Number of pages12
JournalBlood
Volume121
Issue number7
DOIs
StatePublished - Feb 14 2013

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T-cells
HIV Infections
HIV-1
Chemical activation
Population
Mucous Membrane
Blood
Mucosal-Associated Invariant T Cells
T-Lymphocyte Subsets
Escherichia coli
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Leeansyah, E., Ganesh, A., Quigley, M. F., Sönnerborg, A., Andersson, J., Hunt, P. W., ... Sandberg, J. K. (2013). Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood, 121(7), 1124-1135. https://doi.org/10.1182/blood-2012-07-445429

Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. / Leeansyah, Edwin; Ganesh, Anupama; Quigley, Máire F.; Sönnerborg, Anders; Andersson, Jan; Hunt, Peter W.; Somsouk, Ma; Deeks, Steven G.; Martin, Jeffrey N.; Moll, Markus; Shacklett, Barbara; Sandberg, Johan K.

In: Blood, Vol. 121, No. 7, 14.02.2013, p. 1124-1135.

Research output: Contribution to journalArticle

Leeansyah, E, Ganesh, A, Quigley, MF, Sönnerborg, A, Andersson, J, Hunt, PW, Somsouk, M, Deeks, SG, Martin, JN, Moll, M, Shacklett, B & Sandberg, JK 2013, 'Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection', Blood, vol. 121, no. 7, pp. 1124-1135. https://doi.org/10.1182/blood-2012-07-445429
Leeansyah, Edwin ; Ganesh, Anupama ; Quigley, Máire F. ; Sönnerborg, Anders ; Andersson, Jan ; Hunt, Peter W. ; Somsouk, Ma ; Deeks, Steven G. ; Martin, Jeffrey N. ; Moll, Markus ; Shacklett, Barbara ; Sandberg, Johan K. / Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. In: Blood. 2013 ; Vol. 121, No. 7. pp. 1124-1135.
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