The immunotherapeutic role of regulatory T cells in Leishmania (Viannia) panamensis infection

Journal of Immunology

Volumn 193, Issue 6, 2014, Pages 2961-2970

  Ehrlich, Allison ^a   Castilho, Tiago Moreno ^a   Goldsmith Pestana, Karen ^a   Chae, Wook Jin ^b   Bothwell, Alfred L M ^b   Sparwasser, Tim ^c   McMahon Pratt, Diane ^a  

^a YALE UNIVERSITY   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; CD4 ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 2 ANTIBODY; RECOMBINANT INTERLEUKIN 2; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; ANTIGEN ANTIBODY COMPLEX; IL10 PROTEIN, MOUSE; INDOLEAMINE 2,3 DIOXYGENASE; INTERLEUKIN 2; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL EXPANSION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE EXACERBATION; FEMALE; IMMUNOREGULATION; INFECTION CONTROL; LEISHMANIA PANAMENSIS; LYMPHOCYTE FUNCTION; MOLECULAR PATHOLOGY; MOUSE; NONHUMAN; PARASITE LOAD; PROTEIN EXPRESSION; PROTEIN SYNTHESIS REGULATION; REGULATORY T LYMPHOCYTE; SKIN LEISHMANIASIS; ADOPTIVE IMMUNOTHERAPY; ANIMAL; ANTAGONISTS AND INHIBITORS; ANTIGEN ANTIBODY COMPLEX; BAGG ALBINO MOUSE; BIOSYNTHESIS; IMMUNOLOGY; INFLAMMATION; LEISHMANIA; LEISHMANIASIS, MUCOCUTANEOUS; LYMPHOCYTE COUNT; PARASITOLOGY; THERAPEUTIC USE; TRANSGENIC MOUSE; TRANSPLANTATION;

ANIMALS; ANTIBODIES; ANTIGEN-ANTIBODY COMPLEX; CELL PROLIFERATION; FEMALE; IMMUNOTHERAPY, ADOPTIVE; INDOLEAMINE-PYRROLE 2,3,-DIOXYGENASE; INFLAMMATION; INTERFERON-GAMMA; INTERLEUKIN-10; INTERLEUKIN-13; INTERLEUKIN-17; INTERLEUKIN-2; LEISHMANIA GUYANENSIS; LEISHMANIASIS, MUCOCUTANEOUS; LYMPHOCYTE COUNT; MICE; MICE, INBRED BALB C; MICE, TRANSGENIC; PARASITE LOAD; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA;

EID: 84907073956     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1400728     Document Type: Article

References (87)

1. Ban? uls, A. L., M. Hide, and F. Prugnolle. 2007. Leishmania and the leishmaniases: a parasite genetic update and advances in taxonomy, epidemiology and pathogenicity in humans. Adv. Parasitol. 64: 1-109
2. Lipoldová, M., and P. Demant. 2006. Genetic susceptibility to infectious disease: lessons from mouse models of leishmaniasis. Nat. Rev. Genet. 7: 294-305
3. Varela, M., R. E., D. L. Mun?oz, S. M. Robledo, B. K. Kolli, S. Dutta, K. P. Chang, and C. Muskus. 2009. Leishmania (Viannia) panamensis: an in vitro assay using the expression of GFP for screening of antileishmanial drug . Exp. Parasitol. 122: 134-139
4. Osorio, L. E., C. M. Castillo, and M. T. Ochoa. 1998. Mucosal leishmaniasis due to Leishmania (Viannia) panamensis in Colombia: clinical characteristics. Am. J. Trop. Med. Hyg. 59: 49-52
5. McMahon-Pratt, D., and J. Alexander. 2004. Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease? Immunol. Rev. 201: 206-224
6. Ahmed, S., M. Colmenares, L. Soong, K. Goldsmith-Pestana, L. Munstermann, R. Molina, and D. McMahon-Pratt. 2003. Intradermal infection model for pathogenesis and vaccine studies of murine visceral leishmaniasis. Infect. Immun. 71: 401-410
7. Nylén, S., and S. Gautam. 2010. Immunological perspectives of leishmaniasis. J. Glob. Infect. Dis. 2: 135-146
8. Kaye, P., and P. Scott. 2011. Leishmaniasis: complexity at the host-pathogen interface. Nat. Rev. Microbiol. 9: 604-615
9. Castilho, T. M., K. Goldsmith-Pestana, C. Lozano, L. Valderrama, N. G. Saravia, and D. McMahon-Pratt. 2010. Murine model of chronic L. (Viannia) panamensis infection: role of IL-13 in disease. Eur. J. Immunol. 40: 2816-2829
10. Faria, D. R., P. E. Souza, F. V. Dura?es,E. M. Carvalho,K. J. Gollob, P.R.Machado, and W. O. Dutra. 2009. Recruitment of CD8(+) T cells expres sing granzyme A is associated with lesion progression in human cutaneous leishmaniasis. Parasite Immunol. 31: 432-439
11. Novoa, R., O. Bacellar, M. Nascimento, T. M. Cardoso, R. Ramasawmy, W. N. Oliveira, A. Schriefer, and E. M. Carvalho. 2011. IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L. braziliensis Infection. Parasite Immunol. 33: 132-136
12. Faria, D. R., K. J. Gollob, J. Barb osa, Jr., A. Schriefer, P. R. Machado, H. Lessa, L. P. Carvalho, M. A. Romano-Silva, A. R. de Jesus, E. M. Carvalho, and W. O. Dutra. 2005. Decreased in situ expression of interleukin-10 receptor is correlated with the exacerbated inflammatory and cytotoxic responses observed in mucosal leishmaniasis. Infect. Immun. 73: 7853-7859
13. Bacellar, O., H. Lessa, A. Schriefer, P. Machado, A. Ribeiro de Jesus, W. O. Dutra, K. J. Gollob, and E. M. Carvalho. 2002. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infect. Immun. 70: 6734-6740
14. Carvalho, L. P., S. Passos, O. Bacellar, M. Lessa, R. P. Almeida, A. Magalha?es, W. O. Dutra, K. J. Gollob, P. Machado, and A. R. de Jesus. 2007. Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis. Parasite Immunol. 29: 251-258
15. Ribeiro de Jesus, A., T. Luna, R. Pacheco de Almeida, P. R. Machado, and E. M. Carvalho. 2008. Pentoxifylline down modulate in vitro T cell responses and attenuate pathology in Leishmania and HTLV-I infections. Int. Immunopharmacol. 8: 1344-1353
16. Antonelli, L. R., W. O. Dutra, R. P. Almeida, O. Bacellar, and K. J. Gollob. 2004. Antigen spec ific correlations of cellular immune responses in human leishmaniasis suggests mechanisms for immunoregulation. Clin. Exp. Immunol. 136: 341-348
17. Ribeiro-de-Jesus, A., R. P. Almeida, H. Lessa, O. Bacellar, and E. M. Carvalho. 1998. Cytokine profile and pathology in human leishmaniasis. Braz. J. Med. Biol. Res. 31: 143-148
18. Deaglio, S., K. M. Dwyer, W. Gao, D. Friedman, A. Usheva, A. Era t, J. F. Chen, K. Enjyoji, J. Linden, M. Oukka, et al. 2007. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204: 1257-1265
19. Josefowicz, S. Z., L. F. Lu, and A. Y. Rudensky. 2012. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30: 531-564.
20. Mendez S.,S. K. Reckling,C. A. Piccirillo,D. Sacks,Y. Belkaid, 2004, Role for CD4(+) 25(+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J. Exp. Med, 200,201-210.
21. Gupta, G., S. Majumdar, A. Adhikari, P. Bhattacharya, A. K. Mukherjee, S. B. Majumdar, and S. Majumdar. 2011. Treatment with IP-10 induces hostprotective immune response by regulating the T regulatory cell f unctioning in Leishmania donovani-infected mice. Med. Microbiol. Immunol. (Berl.) 200: 241-253
22. Martin, S., R. Agarwal, G. Murugaiyan, and B. Saha. 2010. CD40 expression levels modulate regulatory T cells in Leishmania donovani infection. J. Immunol. 185: 551-559
23. Ji, J., J. Masterson, J. Sun, and L. Soong. 2005. CD4+CD25+ regulatory T cells restrain pathogenic responses during Leishmania amazonensis infection. J. Immunol. 174: 7147-7153
24. Campanelli, A. P., A. M. Roselino, K. A. Cavassani, M. S. Pereira, R. A. Mortara, C. I. Brodskyn, H. S. Goncalves, Y. Belkaid, M. Barral-Netto, A. Barral, and J. S. Silva. 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
25. Costa, D. L., L. H. Guimara ?es, T. M. Cardoso, A. Queiroz, E. Lago, A. M. Roselino, O. Bacellar, E. M. Carvalho, and J. S. Silva. 2013. Characterization of regulatory T cell (Treg) function in patients infected with Leishmania braziliensis. Hum. Immunol. 74: 1491-1500
26. de-Campos, S. N., C. Souza-Lemos, A. Teva, R. Porrozzi, and G. Grimaldi, Jr. 2010. Systemic and compartmentalised imm une responses in a Leishmania braziliensis-macaque model of self-healing cutaneous leishmaniasis. Vet. Immunol. Immunopathol. 137: 149-154
27. C Falca? o, S., T. R. de Moura, J. Clarêncio, C. Brodskyn, A. Barral, and C. I. de Oliveira. 2012. The presence of Tregs does not preclude immunity to reinfection with Leishmania braziliensis. Int. J. Parasitol. 42: 771-780
28. Rodriguez-Pinto, D., A. Navas, V. M . Blanco, L. Ramirez, D. Garcerant, A. Cruz, N. Craft, and N. G. Saravia. 2012. Regulatory T cells in the pathogenesis and healing of chronic human dermal leishmaniasis caused by Leishmania (Viannia) species. PLoS Negl. Trop. Dis. 6: e1627.
29. Lahl, K., C. Loddenkemper, C. Drouin, J. Freyer, J. Arnason, G. Eberl, A. Hamann, H. Wagner, J. Huehn, and T. Sparwasser. 2007. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J. Exp. Med. 204: 57-63
30. Hou, D. Y., A. J. Muller, M. D. Sharma, J. DuHadaway, T. Banerjee, M. Johnson, A. L. Mellor, G. C. Prendergast, and D. H. Munn. 2007. Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res. 67: 792-801
31. Lahl, K., and T. Sparwasser. 2011. In vivo depletion of FoxP3+ Tregs using the DEREG mouse model. Methods Mol. Biol. 707: 157-172
32. Schmittgen, T. D., and K . J. Livak. 2008. Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 3: 1101-1108
33. Boyman, O., M. Kovar, M. P. Rubinstein, C. D. Surh, and J. Sprent. 2006. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 311: 1924-1927
34. Diaz-Gonzalez, R., F. M. Kuhlmann, C. Galan-Rodriguez, L. Madeira da Silva, M. Saldivia, C. E. Karver, A. Rodriguez, S. M. Beverley, M. Navarro, and M. P. Pollastri. 2011. The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing. PLoS Negl. Trop. Dis. 5: e1297
35. Bourreau, E., C. Ronet, E. Darcissac, M. C. Lise, D. Sainte Marie, E. Clity, F. Tacchini-Cottier, P. Couppie, and P. Launois. 2009. Intralesional regulatory Tcell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis. Infect. Immun. 77: 1465-1474
36. Peters, N., and D. Sacks. 2006. Immune privilege in sites of chronic infection: Leishmania and regulatory T cells. Immunol. Rev. 213: 159-179
37. Belkaid, Y. 2003. The role of CD4(+)CD25(+) regulatory T cells in Leishmania infection. Expert Opin. Biol. Ther. 3: 875-885
38. Dominguez-Villar, M., C. M. Baecher-Allan, and D. A. Hafler. 2011. Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease. Nat. Med. 17: 673-675
39. Sharma, M. D., L. Huang, J. H. Choi, E. J. Lee, J. M. Wilson, H. Lemos, F. Pan, B. R. Blazar, D. M. Pardoll, A. L. Mellor, et al. 2 013. An inherently bifunctional subset of Foxp3+ T helper cells is controlled by the transcription factor eos. Immunity 38: 998-1012
40. Hall, B. M., G. T. Tran, N. D. Verma, K. M. Plain, C. M. Robinson, M. Nomura, and S. J. Hodgkinson. 2013. Do Natural T Regulatory Cells become Activated to Antigen Specific T Regulatory Cells in Transplantation and in Autoimmunity? Front. Immunol. 4: 208.
41. O'Con nor, R. A.,M. D. Leech,J. Suffner,G. J. Hämmerling, S. M, Anderton, 2010. Myelin-reactive, TGF-b-induced regulatory T cells can be programmed to develop Th1-like effector function but remain less proinflammatory than myeli n-reactive Th1 effectors and can suppress pathogenic T cell clonal expansion in vivo. J. Immunol, 185, 7235-7243.
42. Schmitt, E. G., and C. B. Williams. 2013. Generation and function of induced regulatory T cells. Front. Immunol. 4: 152
43. Hirahara, K., A. Poholek, G. Vahedi, A. Laurence, Y. Kanno, J. D. Milner, and J. J. O'Shea. 2013. Mechanisms underlying helper T-cell plasticity: impli cations for immune-mediated disease. J. Allergy Clin. Immunol. 131: 1276-1287
44. Wohlfert, E., and Y. Belkaid. 2010. Plasticity of T reg at infected sites. Mucosal Immunol. 3: 213-215
45. Esposito, M., F. Ruffini, A. Bergami, L. Garzetti, G. Borsellino, L. Battistini, G. Martino, and R. Furlan. 2010. IL-17-and IFN-g-secreting Foxp3+ T cells infiltrate the target tissue in experimental autoimmun ity. J. Immunol. 185: 7467-7473
46. Oldenhove, G., N. Bouladoux, E. A. Wohlfert, J. A. Hall, D. Chou, L. Dos Santos, S. O'Brien, R. Blank, E. Lamb, S. Natarajan, et al. 2009. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 31: 772-786
47. Mellor, A. 2005. Indoleamine 2,3 dioxygenase and regulation of T cell immunity. Biochem. Biophys. Res. Commun. 338: 20-24
48. Curti, A., S. Pandolfi, B. Valzasina, M. Aluigi, A. Isidori, E. Ferri, V. Salvestrini, G. Bonanno, S. Rutella, I. Durelli, et a l. 2007. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25-into CD25+ T regulatory cells. Blood 109: 2871-2877
49. Hoshino, S., A. Kurishima, M. Inaba, Y. Ando, T. Fukui, K. Uchida, A. Nishio, H. Iwai, T. Yokoi, T. Ito, et al. 2011. Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced col itis in mice by immunoregulatory dendritic cells. J. Gastroenterol. 46: 1368-1381
50. O'Connor, J. C., M. A. Lawson, C. André, E. M. Briley, S. S. Szegedi, J. Lestage, N. Castanon, M. Herkenham, R. Dantzer, and K. W. Kelley. 2009. Induction of IDO by bacille Calmette-Gué rin is responsible for development of murine depressive-like behavior. J. Immunol. 182: 3202-3212
51. Gu, T., R. B. Ro wswell-Turner, M. O. Kilinc, and N. K. Egilmez. 2010. Central role of IFNgamma-indoleamine 2,3-dioxygenase axis in regulation of interleukin-12-mediated antitumor immunity. Cancer Res. 70: 129-138
52. X u, D., H. Liu, M. Komai-Koma, C. Campbell, C. McSharry, J. Alexander, and F. Y. Liew. 2003. CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and Th2 cells, Leishmania major infection, and coli tis in mice. J. Immunol. 170: 394-399
53. Baban, B., P. R. Chandler, M. D. Sharma, J. Pihkala, P. A. Koni, D. H. Munn, and A. L. Mellor. 2009. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J. Immunol. 183: 2475-2483
54. Fox, J. M., L. K. Sage, L. Huang, J. Barber, K. D. Klonowski, A. L. Mellor, S. M. Tompkins, and R. A. Tripp. 2013. Inhibition of indoleamine 2,3-dioxygenase enhances the T-cell response to influenza virus infection. J. Gen. Virol. 94: 1451-1461
55. Prendergast, G. C., C. Smith, S. Thomas, L. Mandik-Nayak, L. Laury-Kleintop, R. Metz, and A. J. Muller. 2014. Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer. Cancer Immunol. Immunother. 63: 721-735
56. V incendeau, P., S. Lesthelle, A. Bertazzo, M. C. Okomo-Assoumou, G. Allegri, and C. V. Costa. 1999. Importance of L-tryptophan metabolism in trypanosomiasis. Adv. Exp. Med. Biol. 467: 525-531
57. Steiger, R. F., and E. Steiger. 1977. Cultivation of Leishmania donovani and Leishmania braziliensis in defined media: nutritional requirements. J. Protozool. 24: 437-441
58. Murray, H. W., A. S zuro-Sudol, D. Wellner, M. J. Oca, A. M. Granger, D. M. Libby, C. D. Rothermel, and B. Y. Rubin. 1989. Role of tryptophan degradation in respiratory burst-independent antimicrobial activity of gamma interferon-stimulated hu man macrophages. Infect. Immun. 57: 845-849
59. Chapman, T. J., and S. N. Georas. 2013. Adjuvant effect of diphtheria toxin after mucosal administration in both wild type and diphtheria toxin receptor engineered mouse strains. J. Immunol. Methods 400-401: 122-126
60. Christiaansen, A. F., P. M. Boggiatto, and S. M. Varga. 2014. Limitations of Foxp3(+) Treg depletion following viral infection in DEREG mice. J. Immunol. Methods 406: 58-65
61. Gill, D. M. 1982. Bacterial toxins: a table of lethal amounts. Microbiol. Rev. 46: 86-94
62. Lé tourneau, S., E. M. van Leeuwen, C. Krieg, C. Martin, G. Pantaleo, J. Sprent, C. D. Surh, and O. Boyman. 2010. IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. Proc. Natl. Acad. Sci. USA 107: 2171-2176.
63. Webster K. E.,S. Walters,R. E. Kohler,T. Mrkvan,O. Boyman,C. D. Surh,S. T. Grey,J. Sprent, 2009, In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J. Exp. Med, 206, 751-760.
64. Lee, S. Y., M. L. Cho, H. J. Oh, J. G. Ryu, M. J. Park, J. Y. Jhun, M. K. Park, J. C. Stone, J. H. Ju, S. Y. Hwang, et al. 2012. Interleukin-2/anti-interleukin-2 monoclonal antibody immune complex suppre sses collagen-induced arthritis in mice by fortifying interleukin-2/STAT5 signalling pathways. Immunology 137: 305-316
65. Belkaid, Y. 2008. Role of Foxp3-positive regulatory T cells during infection. Eur. J. Immunol. 38: 918-921
66. Rowe, J. H., J. M. Ertelt, and S. S. Way. 2012. Foxp3(+) regulatory T cells, immune stimulation and host defence against infection. Immunology 136: 1-10
67. Berod, L., F. Puttur, J. Huehn, and T. Sparwasser. 2012. Tregs in infection and vaccinology: heroes or traitors? Microb. Biotechnol. 5: 260-269
68. Veiga-Parga, T., A. Suryawanshi, S. Mulik, F. Giménez, S. Sharma, T. Sparwasser, and B. T. Rouse. 2012. On the role of regulatory T cells during viral-induced inflammatory lesions. J. Immunol. 189: 5924-5933
69. Steeg, C., G. Adler, T. Sparwasser, B. Fleischer, and T. Jacobs. 2009. Limited role of CD4+Foxp3+ regulatory T cells in the control of experimental cerebral malaria. J. Immunol. 183: 7014-7022
70. Abel, S., N. Lückheide, A. M. Westendorf, R. Geffers, A. Roers, W. Müller, T. Sparwasser, K. Matuschewski, J. Buer, andW. Hansen. 2012. Strong impact of CD4+ Foxp3+ regulatory T cells and limited effect of T cell-derived IL-1 0 on pathogen clearance during Plasmodium yoelii infection. J. Immunol. 188: 5467-5477
71. Alexander, J., and F. Brombacher. 2012. T helper1/t helper2 cells and resistance/susceptibility to leishmania infection: is this paradigm still relevant? Front. Immunol. 3, 80.
72. Soong, L., C. A. Henard, and P. C. Melby. 2012. Immunopathogenesis of nonhealing American cutaneous leishmaniasis and progressive visceral leishmaniasis. Semin. Immunopathol. 34: 735-751
73. Aseffa, A., A. Gumy, P. Launois, H. R. MacDonald, J. A. Louis, and F. Tacchini-Cottier. 2002. The early IL-4 response to Leishmania major and the resulting Th2 cell maturation steering progressive disease in BALB/c mice are subject to the control of regulatory CD4+CD25+ T cells. J. Immunol. 169: 3232-3241
74. Makala, L. H., B. Baban, H. Lemos, A. R. El-Awady, P. R. Chandler, D. Y. Hou, D. H. Munn, and A. L. Mellor. 2011. Leishmania major attenuates host immunity by stimulating local indoleamine 2,3-dioxygenase expression. J. Infect. Dis. 203: 715-725
75. Soong, L., C. H. Chang, J. Sun, B. J. Longley, Jr., N. H. Ruddle, R. A. Flavell, and D. McMahon-Pratt. 1997. Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection. J. Immunol. 158: 5374 -5383
76. Kima, P. E., S. L. Constant, L. Hannum, M. Colmenares, K. S. Lee, A. M. Haberman, M. J. Shlomchik, and D. McMahon-Pratt. 2000. Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis. J. Exp. Med. 191: 1063-1068
77. Gomes-Silva, A., R. de Cássia Bittar, R. Dos Santos Nogueira, V. S. Amato, M. da Silva Mattos, M. P. Oliveira-Neto, S. G. Coutinho, and A. M. Da-Cruz. 2007. Can interferon-gamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection? Clin. Exp. Immunol. 149: 440-444
78. Morgado, F. N., A. Schubach, C. M. Rosalino, L. P. Quintella, G. Santos, M. Salgueiro, and F. Conceiça? o-Silva. 2008. Is the in situ inflammatory reaction an important tool to understand the cellular immune response in American tegumentary leishmaniasis? Br. J. Dermatol. 158: 50-58
79. Fallarino, F., U. Grohmann, and P. Puccetti. 2012. Indoleamine 2,3-dioxygenase: from catalyst to signaling function. Eur. J. Immunol. 42: 1932- 1937
80. Orabona, C., M. T. Pallotta, and U. Grohmann. 2012. Different partners, opposite outcomes: a new perspective of the immunobiology of indoleamine 2,3-dioxygenase. Mol. Med. 18: 834-842
81. Donovan, M. J., V. Tripathi, M. A. Favila, N. S. Geraci, M. C. Lange, W. Ballhorn, and M. A. McDowell. 2012. Indoleamine 2,3-dioxygenase (IDO) induced by Leishmania infection of human dendritic cells. Par asite Immunol. 34: 464-472
82. Laurence, A., C. M. Tato, T. S. Davidson, Y. Kanno, Z. Chen, Z. Yao, R. B. Blank, F. Meylan, R. Siegel, L. Hennighausen, et al. 2007. Interl eukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26: 371-381
83. Ramirez, C., Y. Diaz-Toro, J. Tellez, T. M. Castilho, R. Rojas, N. A. Ettinger, I. Tikhonova, N. D. Alexander, L. Valderrama, J. Hager, M. E. Wilson, A. Lin, H. Zhao, N. G. Saravia, and D. McMahon-Pratt. 2012. Human macrophage response to L. (Viannia) panamensis: microarray evidence for an early inflammatory respons e. PLoS Negl. Trop. Dis. 6: e1866.
84. Campbell D.J.,M.A. Koch, 2011. Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat. Rev. Immunol, 11, 119-130.
85. Duhen, T., R. Duhen, A. Lanzavecchia, F. Sallusto, and D. J. Campbell. 2012. Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells. Blood 119: 4430-4440
86. Pesenacker, A. M., D. Bending, S. Ursu, Q. Wu, K. Nistala, and L. R. Wedderburn. 2013. CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines. Blood 121: 2647-2658.
87. Koch, M. A., G. Tucker-Heard, N. R. Perdue, J. R. Killebrew, K. B. Urdahl, and D. J. Campbell. 2009. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 infla mmation. Nat. Immunol. 10: 595-602