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Infection and Immunity, April 2009, p. 1465-1474, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01398-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Intralesional Regulatory T-Cell Suppressive Function during Human Acute and Chronic Cutaneous Leishmaniasis Due to Leishmania guyanensis{triangledown}

E. Bourreau,1,{dagger} C. Ronet,2,{dagger} E. Darcissac,1 M. C. Lise,1 D. Sainte Marie,3 E. Clity,3 F. Tacchini-Cottier,2 P. Couppie,3 and P. Launois1,2*

Immunologie des Leishmanioses, Institut Pasteur de la Guyane, 97306 Cayenne, French Guyana,1 WHO-IRTC, Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland,2 Institut Guyanais de Dermatologie Tropicale, E.A. 2188, Centre Hospitalier Andrée Rosemon, 97300 Cayenne, French Guyana3

Received 14 November 2008/ Returned for modification 2 January 2009/ Accepted 11 January 2009

The levels of regulatory T cells (Treg cells), analyzed by Foxp3 mRNA expression, were determined in lesions from patients with acute cutaneous leishmaniasis (ACL) and chronic cutaneous leishmaniasis (CCL). We demonstrated that Treg cells preferentially accumulate in lesions from ACL patients during the early phase of infection (lesion duration of less than 1 month). In addition, levels of Foxp3 mRNA transcripts were significantly higher in specimens from patients with CCL than in those from patients with ACL, suggesting a critical role of intralesional Treg cells in CCL. Intralesional Treg cells from both ACL and CCL patients were shown to have suppressive functions in vitro, since they inhibited the gamma interferon (IFN-{gamma}) produced by CD4+ CD25 T cells purified from peripheral blood mononuclear cells from the same patient in response to Leishmania guyanensis stimulation. Intralesional 2,3-indoleamine dioxygenase (IDO) mRNA expression was associated with that of Foxp3, suggesting a role for IDO in the suppressive activity of intralesional Treg cells. In addition, a role, albeit minor, of interleukin-10 (IL-10) was also demonstrated, since neutralization of IL-10 produced by intralesional T cells increased IFN-{gamma} production by effector cells in an in vitro suppressive assay. These results confirm the role of intralesional Treg cells in the immunopathogenesis of human Leishmania infection, particularly in CCL patients.


* Corresponding author. Mailing address: WHO-IRTC, Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland. Phone: 41 21 692 5703. Fax: 41 21 692 5705. E-mail: plaunois{at}unil.ch

{triangledown} Published ahead of print on 21 January 2009.

Editor: W. A. Petri, Jr.

{dagger} E.B. and C.R. contributed equally to this work.


Infection and Immunity, April 2009, p. 1465-1474, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01398-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.