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RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Ridley DS, Jopling WH, 1966. Classification of leprosy according to immunity: a five-group system. Int J Lepr 34: 255– 273.
-
2.
Montoya D, Modlin RL, 2010. Learning from leprosy: insight into the human innate immune response. Adv Immunol 105: 1– 24.
-
3.
Modlin RL, Mehra V, Wong L, Fujimiya Y, Chang WC, Horwitz DA, Bloom BR, Rea TH, Pattengale PK, 1986. Suppressor T lymphocytes from lepromatous leprosy skin lesions. J Immunol 137: 2831– 2834.
-
4.
Sakaguchi S, Miyara M, Costantino CM, Hafler DA, 2010. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10: 490– 500.
-
5.
Shevach EM, 2009. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 30: 636– 645.
-
6.
Kuhn A, Beissert S, Krammer PH, 2009. CD4(+)CD25 (+) regulatory T cells in human lupus erythematosus. Arch Dermatol Res 301: 71– 81.
-
7.
Antiga E, Quaglino P, Bellandi S, Volpi W, Del Bianco E, Comessatti A, Osella-Abate S, De Simone C, Marzano A, Bernengo MG, Fabbri P, Caproni M, 2010. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol 162: 1056– 1063.
-
8.
Engler JB, Undeutsch R, Kloke L, Rosenberger S, Backhaus M, Schneider U, Egerer K, Dragun D, Hofmann J, Huscher D, Burmester GR, Humrich JY, Enghard P, Riemekasten G, 2011. Unmasking of autoreactive CD4 T cells by depletion of CD25 regulatory T cells in systemic lupus erythematosus. Ann Rheum Dis 70: 2176– 2183.
-
9.
Guyot-Rovol V, Innes JA, Hackforth S, 2006. Regulatory T cells are expanded in blood and disease sites in tuberculosis patients. Am J Respir Crit Care Med 173: 803– 810.
-
10.
Campanelli AP, Roselino AM, Cavassani KA, Pereira MSF, Mortara RA, Brodskyn CI, Goncalves HS, Belkaid Y, Barral-Netto M, Barral A, Silva JS, 2006. CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. J Infect Dis 193: 1313– 1322.
-
11.
Silva LC, Silveira GG, Arnone M, Romiti R, Geluk A, Franken KC, Duarte AJ, Takahashi MD, Benard G, 2010. Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area. Arch Dermatol Res 302: 255– 262.
-
12.
Cavassani KA, Campanelli AP, Moreira AP, Vancim JO, Vitali LH, Mamede RC, Martinez R, Silva JS, 2006. Systemic and local characterization of regulatory T cells in a chronic fungal infection in humans. J Immunol 177: 5811– 5818.
-
13.
Herzenberg LA, Tung J, Moore WA, Herzenberg LA, Parks DR, 2006. Interpreting flow cytometry data: a guide for the perplexed. Nat Immunol 7: 681– 685.
-
14.
Pagliari C, Fernandes ER, Stegun FW, da Silva WL, Duarte MIS, Sotto MN, 2011. Paracoccidioidomycosis: cells expressing IL17 and Foxp3 in cutaneous and mucosal lesions. Microb Pathog 50: 263– 267.
-
15.
Baecher-Allan C, Hafler DA, 2004. Suppressor T cells in human diseases. J Exp Med 200: 273– 276.
-
16.
Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL, 2002. Role for CD4(+) CD25(+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. Nature 420: 502– 507.
-
17.
Bourreau E, Ronet C, Darcissac E, Lise MC, Sainte Marie D, Clity E, Tacchini-Cottier F, Couppie P, Launois P, 2009. Intralesional regulatory T-cell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis. Infect Immun 77: 1465– 1474.
-
18.
Maurya R, Kumar R, Prajapati VK, Manandhar KD, Sacks D, Sundar S, Nylén S, 2010. Human visceral leishmaniasis is not associated with expansion or accumulation of Foxp3+ CD4 cells in blood or spleen. Parasite Immunol 32: 479– 483.
-
19.
Katara GK, Ansari NA, Verma S, Ramesh V, Salotra P, 2011. Foxp3 and IL-10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (PKDL) patients. PLoS Negl Trop Dis 5: e1171.
-
20.
Ismail A, Gadir AF, Theander TG, Kharazmi A, El Hassan AM, 2006. Pathology of post-kala-azar dermal leishmaniasis: a light microscopical, immunohistochemical, and ultrastructural study of skin lesions and draining lymph nodes. J Cutan Pathol 33: 778– 787.
-
21.
Attia EA, Abdallah M, Saad AA, Afifi A, El Tabbakh A, El-Shennawy D, Ali HB, 2010. Circulating CD4+ CD25 high FoxP3+T cells vary in different clinical forms of leprosy. Int J Dermatol 49: 1152– 1158.
-
22.
Massone C, Nunzi E, Ribeiro-Rodrigues R, Talhari C, Talhari S, Schettini AP, Parente JN, Brunasso AM, Puntoni M, Clapasson A, Noto S, Cerroni L, 2010. T regulatory cells and plasmocytoid dendritic cells in Hansen disease: a new insight into pathogenesis? Am J Dermatopathol 32: 251– 256.
-
23.
Epple HJ, Loddenkemper C, Kunkel D, Tröger H, Maul J, Moos V, Berg E, Ullrich R, Schulzke JD, Stein H, Duchmann R, Zeitz M, Schneider T, 2006. Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood 108: 3072– 3078.
-
24.
Longley J, Haregewoin A, Yemaneberhan T, Warndorff van Diepen T, Nsibami J, Knowles D, Smith KA, Godal T, 1985. In vivo responses to Mycobacterium leprae: antigen presentation, interleukin-2 production, and immune cell phenotypes in naturally occurring leprosy lesions. Int J Lepr Other Mycobact Dis 53: 385– 394.
-
25.
Haregewoin A, Longley J, Bjune G, Mustafa AS, Godal T, 1985. The role of interleukin-2 (IL-2) in the specific unresponsiveness of lepromatous leprosy to Mycobacterium leprae: studies in vitro and in vivo. Immunol Lett 11: 249– 252.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 219 | 197 | 19 |
| Full Text Views | 364 | 6 | 0 |
| PDF Downloads | 122 | 4 | 0 |
Increased Expression of Regulatory T Cells and Down-Regulatory Molecules in Lepromatous Leprosy
Maria L. Palermo
Maria L. Palermo
Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Health Institute, São Paulo State Health Department, Sao Paulo, Brazil; Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil; Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil
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Carla Pagliari
Carla Pagliari
Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Health Institute, São Paulo State Health Department, Sao Paulo, Brazil; Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil; Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil
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Maria Angela B. Trindade
Maria Angela B. Trindade
Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Health Institute, São Paulo State Health Department, Sao Paulo, Brazil; Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil; Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil
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Tania M. Yamashitafuji
Tania M. Yamashitafuji
Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Health Institute, São Paulo State Health Department, Sao Paulo, Brazil; Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil; Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil
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Alberto José S. Duarte
Alberto José S. Duarte
Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Health Institute, São Paulo State Health Department, Sao Paulo, Brazil; Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil; Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil
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Camila R. Cacere
Camila R. Cacere
Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Health Institute, São Paulo State Health Department, Sao Paulo, Brazil; Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil; Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil
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Gil Benard
Gil Benard
Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; Health Institute, São Paulo State Health Department, Sao Paulo, Brazil; Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil; Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil
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T regulatory cells (Tregs) play an important role in the mechanism of host's failure to control pathogen dissemination in severe forms of different chronic granulomatous diseases, but their role in leprosy has not yet been elucidated; 28 newly diagnosed patients (16 patients with lepromatous leprosy and 12 patients with tuberculoid leprosy) and 6 healthy Mycobacterium leprae-exposed individuals (contacts) were studied. Tregs were quantified by flow cytometry (CD4+ CD25+ Foxp3+) in peripheral blood mononuclear cells stimulated in vitro with a M. leprae antigenic preparation and phytohemagglutinin as well as in skin lesions by immunohistochemistry. The lymphoproliferative (LPR), interleukin-10 (IL-10), and interferon-γ (IFN-γ) responses of the in vitro-stimulated peripheral blood mononuclear cells and the in situ expression of IL-10, transforming growth factor-β (TGF-β), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) were also determined. We show that M. leprae antigens induced significantly lower LPR but significantly higher Treg numbers in lepromatous than tuberculoid patients and contacts. Mitogen-induced LPR and Treg frequencies were not significantly different among the three groups. Tregs were also more frequent in situ in lepromatous patients, and this finding was paralleled by increased expression of the antiinflammatory molecules IL-10 and CTLA-4 but not TGF-β. In lepromatous patients, Tregs were intermingled with vacuolized hystiocyte infiltrates all over the lesion, whereas in tuberculoid patients, Tregs were rare. Our results suggest that Tregs are present in increased numbers, and they may have a pathogenic role in leprosy patients harboring uncontrolled bacillary multiplication but not in those individuals capable of limiting M. leprae growth.
Author Notes
Financial support: This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Pesquisa Científica, and Coordenação de Aprimoramento de Pessoal de Nível Superior.
Authors' addresses: Maria L. Palermo and Camila R. Cacere, Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil, E-mails: luli_neves@yahoo.com.br and cacerec@hotmail.com. Carla Pagliari, Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil, E-mail: cpagliari@usp.br. Maria Angela B. Trindade, Health Institute, São Paulo State Health Department, Sao Paulo, Brazil, E-mail: angelatrindade@uol.com.br. Tania M. Yamashitafuji, Ambulatory of Specialities, São Paulo City Health Service, Sao Paulo, Brazil, E-mail: fernanda_fuji@yahoo.com.br. Alberto José S. Duarte, Laboratory of Medical Investigation Unit 56, Department of Pathology, Medical School, University of Sao Paulo, Sao Paulo, Brazil, E-mail: adjsduar@usp.br. Gil Benard, Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil; and Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, Sao Paulo, Brazil, E-mail: mahong@usp.br.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Ridley DS, Jopling WH, 1966. Classification of leprosy according to immunity: a five-group system. Int J Lepr 34: 255– 273.
-
2.
Montoya D, Modlin RL, 2010. Learning from leprosy: insight into the human innate immune response. Adv Immunol 105: 1– 24.
-
3.
Modlin RL, Mehra V, Wong L, Fujimiya Y, Chang WC, Horwitz DA, Bloom BR, Rea TH, Pattengale PK, 1986. Suppressor T lymphocytes from lepromatous leprosy skin lesions. J Immunol 137: 2831– 2834.
-
4.
Sakaguchi S, Miyara M, Costantino CM, Hafler DA, 2010. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10: 490– 500.
-
5.
Shevach EM, 2009. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 30: 636– 645.
-
6.
Kuhn A, Beissert S, Krammer PH, 2009. CD4(+)CD25 (+) regulatory T cells in human lupus erythematosus. Arch Dermatol Res 301: 71– 81.
-
7.
Antiga E, Quaglino P, Bellandi S, Volpi W, Del Bianco E, Comessatti A, Osella-Abate S, De Simone C, Marzano A, Bernengo MG, Fabbri P, Caproni M, 2010. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol 162: 1056– 1063.
-
8.
Engler JB, Undeutsch R, Kloke L, Rosenberger S, Backhaus M, Schneider U, Egerer K, Dragun D, Hofmann J, Huscher D, Burmester GR, Humrich JY, Enghard P, Riemekasten G, 2011. Unmasking of autoreactive CD4 T cells by depletion of CD25 regulatory T cells in systemic lupus erythematosus. Ann Rheum Dis 70: 2176– 2183.
-
9.
Guyot-Rovol V, Innes JA, Hackforth S, 2006. Regulatory T cells are expanded in blood and disease sites in tuberculosis patients. Am J Respir Crit Care Med 173: 803– 810.
-
10.
Campanelli AP, Roselino AM, Cavassani KA, Pereira MSF, Mortara RA, Brodskyn CI, Goncalves HS, Belkaid Y, Barral-Netto M, Barral A, Silva JS, 2006. CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. J Infect Dis 193: 1313– 1322.
-
11.
Silva LC, Silveira GG, Arnone M, Romiti R, Geluk A, Franken KC, Duarte AJ, Takahashi MD, Benard G, 2010. Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area. Arch Dermatol Res 302: 255– 262.
-
12.
Cavassani KA, Campanelli AP, Moreira AP, Vancim JO, Vitali LH, Mamede RC, Martinez R, Silva JS, 2006. Systemic and local characterization of regulatory T cells in a chronic fungal infection in humans. J Immunol 177: 5811– 5818.
-
13.
Herzenberg LA, Tung J, Moore WA, Herzenberg LA, Parks DR, 2006. Interpreting flow cytometry data: a guide for the perplexed. Nat Immunol 7: 681– 685.
-
14.
Pagliari C, Fernandes ER, Stegun FW, da Silva WL, Duarte MIS, Sotto MN, 2011. Paracoccidioidomycosis: cells expressing IL17 and Foxp3 in cutaneous and mucosal lesions. Microb Pathog 50: 263– 267.
-
15.
Baecher-Allan C, Hafler DA, 2004. Suppressor T cells in human diseases. J Exp Med 200: 273– 276.
-
16.
Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL, 2002. Role for CD4(+) CD25(+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. Nature 420: 502– 507.
-
17.
Bourreau E, Ronet C, Darcissac E, Lise MC, Sainte Marie D, Clity E, Tacchini-Cottier F, Couppie P, Launois P, 2009. Intralesional regulatory T-cell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis. Infect Immun 77: 1465– 1474.
-
18.
Maurya R, Kumar R, Prajapati VK, Manandhar KD, Sacks D, Sundar S, Nylén S, 2010. Human visceral leishmaniasis is not associated with expansion or accumulation of Foxp3+ CD4 cells in blood or spleen. Parasite Immunol 32: 479– 483.
-
19.
Katara GK, Ansari NA, Verma S, Ramesh V, Salotra P, 2011. Foxp3 and IL-10 expression correlates with parasite burden in lesional tissues of post kala azar dermal leishmaniasis (PKDL) patients. PLoS Negl Trop Dis 5: e1171.
-
20.
Ismail A, Gadir AF, Theander TG, Kharazmi A, El Hassan AM, 2006. Pathology of post-kala-azar dermal leishmaniasis: a light microscopical, immunohistochemical, and ultrastructural study of skin lesions and draining lymph nodes. J Cutan Pathol 33: 778– 787.
-
21.
Attia EA, Abdallah M, Saad AA, Afifi A, El Tabbakh A, El-Shennawy D, Ali HB, 2010. Circulating CD4+ CD25 high FoxP3+T cells vary in different clinical forms of leprosy. Int J Dermatol 49: 1152– 1158.
-
22.
Massone C, Nunzi E, Ribeiro-Rodrigues R, Talhari C, Talhari S, Schettini AP, Parente JN, Brunasso AM, Puntoni M, Clapasson A, Noto S, Cerroni L, 2010. T regulatory cells and plasmocytoid dendritic cells in Hansen disease: a new insight into pathogenesis? Am J Dermatopathol 32: 251– 256.
-
23.
Epple HJ, Loddenkemper C, Kunkel D, Tröger H, Maul J, Moos V, Berg E, Ullrich R, Schulzke JD, Stein H, Duchmann R, Zeitz M, Schneider T, 2006. Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood 108: 3072– 3078.
-
24.
Longley J, Haregewoin A, Yemaneberhan T, Warndorff van Diepen T, Nsibami J, Knowles D, Smith KA, Godal T, 1985. In vivo responses to Mycobacterium leprae: antigen presentation, interleukin-2 production, and immune cell phenotypes in naturally occurring leprosy lesions. Int J Lepr Other Mycobact Dis 53: 385– 394.
-
25.
Haregewoin A, Longley J, Bjune G, Mustafa AS, Godal T, 1985. The role of interleukin-2 (IL-2) in the specific unresponsiveness of lepromatous leprosy to Mycobacterium leprae: studies in vitro and in vivo. Immunol Lett 11: 249– 252.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 219 | 197 | 19 |
| Full Text Views | 364 | 6 | 0 |
| PDF Downloads | 122 | 4 | 0 |