16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

TREG CHARACTERIZATION IN SIV INFECTION OF RHESUS MACAQUES

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. WeAa0302

Barbercheck J.¹, Apetrei C.², Ploquin M.³, Butor C.⁴, Muller-Trutwin M.³, Veazey R.¹, Lackner A.⁵, Pandrea I.^1
1 Tulane National Primate Research Center, Comparative Pathology, Covington, LA, United States, ² Tulane National Primate Research Center, Microbiology, Covington, LA, United States, ³ Institut Pasteur, Paris, France, 4 Institut Cochin, CNRS, Paris, France, ⁵ Tulane National Primate Research Center, Covington, LA, United States

BACKGROUND: T regulatory cells (Tregs) may play an important role in HIV/SIV pathogenesis. Different immune activation may explain pathogenicity versus non-pathogenicity. Our aim was to identify and characterize CD4+CD25+ cells in normal rhesus macaques (Rh) and African green monkeys (AGMs), and investigate the in vivo dymanics of Tregs during SIVmac and SIVagm infection.

METHODS: Tregs in 6 Rh and 6 AGMs were immunophenotyped by flow cytometry. CD4+CD25+ T cells were sorted and functional studies were done. PCRs were done on total PBMCs and sorted cells (CD4, CD14 and non-CD4+/non-CD14+) to characterize the expression of Treg marker FOX-P3. Immunohistochemistry determined the expression of FOX-P3 in LN and intestine. The dynamics of Tregs were examined by flow cytometry (CD4+CD25+ T cells) and PCR (FOX-P3) in PBMCs. To determine if the loss of Tregs is due to direct viral lysis, CD4+CD25+ T cells were sorted infected with SIVmac in vitro.

RESULTS: Tregs are suppressive in Rh and AGMs. CD4+CD25+ T cells specifically expressed FOX-P3, the transcription factor observed in mice and humans. FOX-P3 rtPCR on total PBMCs showed the CD4 population accounts for the majority expression of FOX-P3. rtPCR showed RNA levels for FOX-P3 were lower in CD4+ T cells sorted from intestine than peripheral cells.

An increase in CD4+CD25+ T cells was observed during primary infection with SIVmac and SIVagm. CD4+CD25+ T cells showed a significant loss in chronic SIVmac-infected Rh. Tregs were better preserved in chronically SIVagm-infected AGMs. FOX-P3 expression paralleled percentages of CD4+CD25+ T cells. In vitro functional studies showed that sorted CD4+CD25+ T cells are susceptible to SIV infection in Rh.

CONCLUSIONS: Our study demonstrates that these species are good models for studying Tregs' role in HIV infection. Tregs' decrease during SIVmac infection may result in lack of immuneoregulation and aberrant hyperactivation of T cells. The role of Tregs in pathogenicity can only be determined using animal models.

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2006-08-13
WeAa0302

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