Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 632436, 10 pages http://dx.doi.org/10.1155/2013/632436 Research Article CD4 + CD25 + FOXP3 + Treg Cells Induced by rSSP4 Derived from T. cruzi Amastigotes Increase Parasitemia in an Experimental Chagas Disease Model Y. Flores-García, 1 J. L. Rosales-Encina, 1 V. H. Rosales-García, 2 A. R. Satoskar, 3 and P. Talamás-Rohana 1 1 Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 07360 Mexico, DF, Mexico 2 Unidad de Servicios Generales, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 07360 Mexico City, DF, Mexico 3 Departments of Microbiology and Pathology, Medical Center, e Ohio State University, Colombus, OH 43210, USA Correspondence should be addressed to P. Talamás-Rohana; ptr@cinvestav.mx Received 7 August 2012; Revised 20 October 2012; Accepted 29 October 2012 Academic Editor: Luis I. Terrazas Copyright © 2013 Y. Flores-García et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Currently, there is a considerable controversy over the participation of Treg cells during Trypanosoma cruzi infection, the main point being whether these cells play a negative or a positive role. In this work, we found that the adoptive transfer of CD4 + CD25 + FOXP3 + T cells from rSSP4- (a recombinant Trypanosoma cruzi amastigote derived protein, previously shown to have immunomodulatory properties on macrophages) immunized BALB/c donors into syngenic recipients simultaneously with T. cruzi challenge reduces cardiac in�ammation and prolongs hosts � survival but increases blood parasitemia and parasite loads in the heart. ese CD4 + CD25 + FOXP3 + Treg cells from immunized mice have a relatively TGF--dependent suppressive activity on CD4 + T cells. erefore, regulatory CD4 + CD25 + T cells play a positive role in the development of acute T. cruzi infection by inducing immunosuppressive activity that controls early cardiac in�ammation during acute Chagas disease, prolonging survival, but at the same time promoting parasite growth. 1. Introduction Trypanosoma cruzi is an intracellular protozoan parasite transmitted through the feces of blood-sucking insect vec- tors (Triatoma) and causes Chagas disease [1]. Intracellular amastigotes are responsible for the persistence of T. cruzi infection and induce in�ammatory tissue damage in organs such as the heart, esophagus, and colon [2]. Currently, there is a considerable controversy over the participation of Treg cells during Trypanosoma cruzi infection, the main point being whether these cells play a negative or a positive role. Cytokines produced in response to infection with T. cruzi largely determine the immunopathology and susceptibility to disease. IL-10 and TGF- both are differentiation factors of Treg cells. TGF- production decreases elimination of par- asites by macrophages (MΦs), associated with exacerbation of disease [3]. Similarly, IL-10 has also been associated with susceptibility to T. cruzi infection [4, 5] by blocking the production of IFN- by mouse spleen cells and inhibiting some IFN--induced MΦ killing of intracellular T. cruzi [6, 7]. Parasites actively secrete or express molecules includ- ing parasite-derived proteins, lipids, and glycoconjugates that have potent effects on the immune system [8]. Newly transformed amastigotes, both intracellular and extracellular, express a major surface glycoprotein (SSP4) bound to the plasma membrane by a GPI anchor [9]. e gene that codi�es for this protein was cloned [10], and rSSP4 was shown to be a modulator of the immune response, inducing high levels of IgG1, IgG2a and IgG2b isotypes, and the expression of iNOS and production of NO by MΦs [11]. Moreover, rSSP4 was also able to induce the mRNA for