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Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection

  1. Author:
    Kader, M.
    Bixler, S.
    Piatak, M.
    Lifson, J.
    Mattapallil, J. J.
  2. Author Address

    Mattapallil, J. J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Piatak, M.; Lifson, J.] NCI, SAIC, Frederick, MD 21701 USA.
    1. Year: 2009
  1. Journal: Journal of Medical Primatology
    1. 38
    2. Pages: 32-38
  2. Type of Article: Proceedings Paper
  1. Abstract:

    Background Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th-17 cells (IL-17+CD4+ T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to repopulation of CD4+ T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th-17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th-17 cells that are lost during infection. Methods Dynamics of alpha 4+beta 7hi CD4+ T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th-17 and Tc-17 cells was determined following infection and after therapy. Relative expression of IL-21, IL-23, and TGF beta was determined using Taqman PCR. Results Treatment of SIV infected rhesus macaques with anti-retroviral therapy was associated with a substantial repopulation of mucosal homing alpha 4+beta 7hiCD4+ T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th-17 responses. Interestingly, SIV infection was associated with an increase in Tc-17 responses (IL-17+CD8+ T cells) suggesting to a skewing in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th-17 : Tc-17 responses induced following SIV infection. Conclusions ART was associated with substantial repopulation of alpha 4+beta 7hi CD4+ T cells in peripheral blood with little or no rebound of Th-17 cells. On the other hand, repopulation of alpha 4+beta 7hi CD4+ T cells was accompanied by persistence of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17 and Tc-17 responses likely plays a role in disease progression.

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External Sources

  1. DOI: 10.1111/j.1600-0684.2009.00373
  2. PMID: 19863676

Library Notes

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