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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900852v1 183/6/4103    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Albareda, M. C. Articles by Postan, M. PubMed PubMed Citation Articles by Albareda, M. C. Articles by Postan, M.

Chronic Human Infection with Trypanosoma cruzi Drives CD4⁺ T Cells to Immune Senescence¹

María Cecilia Albareda^*, Gabriela Carina Olivera^*, Susana A. Laucella^*, María Gabriela Alvarez, Esteban Rodrigo Fernandez^*, Bruno Lococo, Rodolfo Viotti, Rick L. Tarleton and Miriam Postan^2,*

^* Instituto Nacional de Parasitología "Dr. M. Fatala Chaben," Buenos Aires, Argentina; Hospital Interzonal General de Agudos "Eva Perón," San Martín, Provincia de Buenos Aires, Argentina; and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602

Previously we found that the frequency of IFN--producing CD8⁺ T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease along with low levels of IL-2-secreting CD8⁺ T cells in all clinical stages. This impairment of the parasite-specific T cell responses was associated with phenotypic features of immune senescence of the CD8⁺ T cell compartment. These data prompted us to address the question of whether the CD4⁺ T cell compartment also experiences signs of exhaustion. Thus, we performed a functional and phenotypical characterization of T. cruzi-specific and overall CD4⁺ T cells in chronically infected subjects with different degrees of cardiac dysfunction. The results show an inverse association between disease severity and the frequency of T. cruzi-specific IFN--producing CD4⁺ T cells. The high expression of CD27 and CD28 with a relative low expression of CD57 found on CD4⁺IFN-⁺ T cells suggests that the effector T cell pool in chronic T. cruzi infection includes a high proportion of newly recruited T cells, but a low frequency of long-term memory cells. The total CD4⁺ T cell compartment shows signs of senescence and later stages of differentiation associated with more severe stages of the disease. These findings support the hypothesis that long-term T. cruzi infection in humans might exhaust long-lived memory T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant 5P01AI044979, National Fund for Science and Technology of Argentina (FONCYT PICT 05-38187), and Ministerio de Salud (Buenos Aires, Argentina). S.L. and M.P. are members of the Scientific Career of Consejo Nacional de Investigación Científica y Técnica.

² Address correspondence and reprint requests to Dr. Miriam Postan, Instituto Nacional de Parasitologia "Dr. M. Fatala Chaben," Buenos Aires, Argentina. E-mail address: miriampostan{at}yahoo.com

³ Abbreviation used in this paper: ECG, electrocardiogram.