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Journal of Virology, August 2008, p. 7422-7431, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00102-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Early Increases in Superantigen-Specific Foxp3+ Regulatory T Cells during Mouse Mammary Tumor Virus Infection{triangledown} ,{dagger}

Gabriel Cabrera,1,{ddagger} Dalia Burzyn,1,{ddagger} Juliana Mundiñano,1 M. Cecilia Courreges,2 Gabriela Camicia,1 Daniela Lorenzo,1 Héctor Costa,1 Susan R. Ross,2 Irene Nepomnaschy,1 and Isabel Piazzon1*

Instituto de Leucemia Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina,1 Department of Microbiology and Abramson Family Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania2

Received 15 January 2008/ Accepted 12 May 2008

Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. Here, we show in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (SAg)-specific Foxp3+ regulatory T cells (Treg) in Peyer's patches (PP). These increases were shown to be dependent on the presence of dendritic cells. CD4+ CD25+ T cells from the PP of infected mice preferentially suppress the proliferative response of T cells to SAg-expressing antigen-presenting cells ex vivo. We investigated the influence of the depletion of CD25+ cells at different stages of the infection. When CD25+ cells were depleted before MMTV infection, an increase in the number of PP SAg-cognate Foxp3– T cells was found at day 6 of infection. Since the SAg response is associated with viral amplification, the possibility exists that Treg cells attenuate the increase in viral load at the beginning of the infection. In contrast, depletion of CD25+ cells once the initial SAg response has developed caused a lower viral load, suggesting that at later stages Treg cells may favor viral persistence. Thus, our results indicated that Treg cells play an important and complex role during MMTV infection.

* Corresponding author. Mailing address: Instituto de Leucemia Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Pacheco de Melo 3081 (1425), Buenos Aires, Argentina. Phone: 54 11 4805 3411, ext. 287. Fax: 54 11 4803 9475. E-mail: ipiazzon{at}hematologia.anm.edu.ar

{triangledown} Published ahead of print on 21 May 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} G. C. and D. B. contributed equally to this work.

Journal of Virology, August 2008, p. 7422-7431, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00102-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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