Details

Autor(en) / Beteiligte

• Kader, M.
• Bixler, S.
• Piatak, M.
• Lifson, J.
• Mattapallil, J.J.

Titel

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

Ist Teil von

• Journal of medical primatology, 2009-10, Vol.38 (s1), p.32-38

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2009

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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 α4+β7hi 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 TGFβ 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 α4+β7hiCD4+ 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 α4+β7hi CD4+ T cells in peripheral blood with little or no rebound of Th‐17 cells. On the other hand, repopulation of α4+β7hi 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.