American tegumentary leishmaniasis: T-cell differentiation profile of cutaneous and mucosal forms—co-infection with Trypanosoma cruzi
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American tegumentary leishmaniasis displays two main clinical forms: cutaneous (CL) and mucosal (ML). ML is more resistant to treatment and displays a more severe and longer evolution. Since both forms are caused by the same Leishmania species, the immunological response of the host may be an important factor determining the evolution of the disease. Herein, we analyzed the differentiation and memory profile of peripheral CD4+ and CD8+ T lymphocytes of patients with CL and ML and their Leishmania–T. cruzi co-infected counterparts. We measured the expression of CD27, CD28, CD45RO, CD127, PD-1 and CD57, together with interferon-γ and perforin. A highly differentiated phenotype was reflected on both T subsets in ML and preferentially on CD8+ T cells in CL. A positive trend toward a higher T differentiation profile was found in T. cruzi-infected CL and ML patients as compared with Leishmania single infections. Association between CD8+ T-cell differentiation and illness duration was found within the first year of infection, with progressive increase of highly differentiated markers over time. Follow-up of patients with good response to therapy showed predominance of early differentiated CD8+ T cells and decrease of highly differentiated cells, while patients with frequent relapses presented the opposite pattern. CD8+ T cells showed the most striking changes in their phenotype during leishmaniasis. Patients with long-term infections showed the highest differentiated degree implying a relation between T differentiation and parasite persistence. Distinct patterns of CD8+ T differentiation during follow-up of different clinical outcomes suggest the usefulness of this analysis in the characterization of Leishmania-infected patients.
KeywordsCutaneous leishmaniasis Mucosal leishmaniasis Peripheral T lymphocytes Differentiation and memory phenotype Leishmania–T. cruzi co-infection
Authors would like to thank Dermatology Service of Hospital Señor del Milagro and Dermatology/Otorhinolaryngology Services of Hospital San Bernardo, Salta, Argentina. We would also like to thank Marta Felippo, Nora Galassi and Norma Riera for bringing their knowledge and help in the flow cytometry acquisition and analyses. We would like to give special thanks to Susana Laucella, for carefully reading and correcting on the entire manuscript.
This work was supported by grants from Bunge & Born Foundation (FBBEI6/08), Alberto J. Roemmers Foundation, René Barón Foundation and National Agency for Scientific and Technological Promotion (FONCYT-PICT-00983), Argentina.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individuals participants included in the study.
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