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Journal of Virology, May 2007, p. 4445-4456, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.00026-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys{triangledown}

L. E. Pereira,1 F. Villinger,1 N. Onlamoon,1,2 P. Bryan,1 A. Cardona,1 K. Pattanapanysat,2,3 K. Mori,4,{dagger} S. Hagen,5 L. Picker,5 and A. A. Ansari1*

Department of Pathology and Lab Medicine, Emory University School of Medicine, Atlanta, Georgia,1 Department of Immunology, Siriraj Hospital, Mahidol University, Bangkok, Thailand,2 Thailand Research Fund,3 Tsukuba Primate Center, NIH, Japan,4 Oregon Health and Science University and Oregon National Primate Research Center, Portland, Oregon5

Received 4 January 2007/ Accepted 12 February 2007

Differences in clinical outcome of simian immunodeficiency virus (SIV) infection in disease-resistant African sooty mangabeys (SM) and disease-susceptible Asian rhesus macaques (RM) prompted us to examine the role of regulatory T cells (Tregs) in these two animal models. Results from a cross-sectional study revealed maintenance of the frequency and absolute number of peripheral Tregs in chronically SIV-infected SM while a significant loss occurred in chronically SIV-infected RM compared to uninfected animals. A longitudinal study of experimentally SIV-infected animals revealed a transient increase in the frequency of Tregs from baseline values following acute infection in RM, but no change in the frequency of Tregs occurred in SM during this period. Further examination revealed a strong correlation between plasma viral load (VL) and the level of Tregs in SIV-infected RM but not SM. A correlation was also noted in SIV-infected RM that control VL spontaneously or in response to antiretroviral chemotherapy. In addition, immunofluorescent cell count assays showed that while Treg-depleted peripheral blood mononuclear cells from RM led to a significant enhancement of CD4+ and CD8+ T-cell responses to select pools of SIV peptides, there was no detectable T-cell response to the same pool of SIV peptides in Treg-depleted cells from SIV-infected SM. Our data collectively suggest that while Tregs do appear to play a role in the control of viremia and the magnitude of the SIV-specific immune response in RM, their role in disease resistance in SM remains unclear.

* Corresponding author. Mailing address: Department of Pathology and Lab Medicine, Emory University School of Medicine, 101 Woodruff Circle, Rm. 2309, Atlanta, GA 30329. Phone: (404) 712-2834. Fax: (404) 712-1771. E-mail: pathaaa{at}emory.edu

{triangledown} Published ahead of print on 21 February 2007.

{dagger} Present address: AIDS Research Center, National Institute of Infectious Disease, Tokyo, Japan.

Journal of Virology, May 2007, p. 4445-4456, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.00026-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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