A Comparative Evaluation of Regulatory T Cells Profile among Acute and Chronic Cutaneous Leishmaniasis Using Flow Cytometry
AbstractBackground: Cutaneous leishmaniasis (CL) is described as a major health problem in many countries of the world. Regulatory T cells (Tregs) are characterized as one of immunologic indexes. One of the best methods to determine of Tregs percentage is flow cytometry. The aim of this study was determination of the role of Tregs profile among acute and chronic forms of human CL using flow cytometry analysis. Methods: This study was conducted on 24 patients referred to Laboratory of Leishmaniasis, Tehran University of Medical Sciences, Tehran, Iran with acute and 14 patients with chronic phases of CL as well as 15 healthy individuals as control group in 2015-2016. After microscopic examination, 2 ml of peripheral blood samples were collected for determining percentage of CD4+ CD25+ CD127 low Tregs by using flow cytometry method. Results: Using flow cytometry analysis, the average percentage of Tregs were calculated 5.73, 6.71 and 6.61 for acute, chronic and healthy individuals, respectively. With SPSS software and Scheffe multiple comparison tests, the differences within in these groups are statistically significant (P=0.04) and between the acute and chronic group, there was marginally significant with approximately 91% of confidence level (P=0.088). Conclusion: Marginally differences were found significantly among averages of Regulatory T cells, acute and chronic phases of CL. Further comprehensive studies can be needed to verify the role of Tregs in both phases of CL cases.
Bittencourt AL, BarralA. Evaluation of histopathological classifications of American cutaneous and mucocutaneousleishmaniasis. Mem Inst Oswaldo Cruz. 1991; 86:51-6.
World Health Organization. Control of the leishmaniases, Technical Report Series 949, Re-port of a meeting of the WHO Expert Committee on the Control of Leishmaniases, 2010; Geneva, 22-26 March.
Mahmoudzadeh-Niknam H, Ajdary S, Riazi-Rad F, Mirzadegan E, et al. Molecular epidemiology of cutaneous leishmaniasis and heterogeneity of Leishmaniamajorstrains in Iran. Trop Med Int Health. 2012; 17:1335-44.
Hepburn NC. Cutaneous leishmaniasis: An overview. J Postgrad Med. 2003; 49:50-4.
Gaafar A, Veress B, Permin H, Kharazmi A, Theander TG, el Hassan AM. Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major. Clin Immunol. 1999; 91:314-20.
Louzir H, Melby PC, Ben Salah A, Marrakchi H, Aoun K, Ben Ismail R, et al. Immunologic determinants of disease evolution in localized cutaneous leishmaniasis due to Leishmania major. J Infect Dis. 1998; 177:1687–95.
Ajdary S, Jafari-Shakib R, Riazi-Rad F, Khamesipour A. Soluble CD26 and CD30 levels in patients with anthroponotic cutaneous leishmaniasis. J Infect. 2007; 55:75-8.
Jafari-Shakib R, Shokrgozar MA, Nassiri-Kashani M, Malakafzali B, Nikbin B, Khamesipour A. Plasma sCD26 and sCD30 levels in cutaneous leishmaniasis. Acta Trop. 2009; 109:61–3.
Passwell JH, Shor R, Shoham J. The enhancing effect of interferon-beta and –gamma on the killing of Leishmania tropica major in human mononuclear phagocytes in vitro. J Immunol. 1986;136:3062-6.
Da Cruz AM, Bittar R, Mattos M, et al. T-cell-mediated immune responses in patients with cutaneous or mucosal leishmaniasis: long-term evaluation after therapy. Clin Diag Lab Immunol. 2002; 9:251-6.
Belkaid Y, Hoffmann KF, Mendez S, et al. The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti–IL-10 receptor antibody for sterile cure. J Exp Med. 2001; 194:1497-506.
Bogdan C, Donhauser N, Doring R. Fibroblasts as host cells in latent leishmaniosis. J Exp Med. 2000; 191:2121-30.
Bacchetta R, Gambineri E, Roncarolo MG. Role of regulatory T cells and FOXP3 in human diseases. J Allergy Clin Immunol. 2007; 120(2):227-35.
Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+CD25-I T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003; 198:1875-86.
Liston A, Gray DH. Homeostatic control of regulatory T cell diversity. Nat Rev Immunol. 2014; 14:154-65.
Mendez, S., S. K. Reckling, C. A. Piccirillo, D. Sacks, and Y. Belkaid. Role for CD4 (+) CD25 (+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J Exp Med.2004; 200(2): 201–10.
Falcão SC, de Moura TR, Clarencio J, Brodskyn C, Barral A, de Oliveira CI. The presence of Tregs does not preclude immunity to reinfection with Leishmaniabraziliensis. Int J Parasitol 2012; 42:771-80.
Nagase H, Jones KM, Anderson CF, Noben-Trauth N. Despite increased CD4+Foxp3+ cells within the infection site, BALB/c IL-4 receptor-deﬁcient mice reveal CD4+Foxp3-negative T cells as a source of IL-10 in Leishmania major susceptibility. J Immunol. 2007; 179:2435-44.
Sufﬁa I, Reckling SK, Salay G, Belkaid Y. A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection. J Immunol. 2005; 174:5444-55.
Rouse BT, Suvas S. Regulatory cells and infectious agents: détentes cordiale and contraire. J Immunol. 2004; 173:2211-5.
Campanelli AP, Roselino AM, Cavassani KA, Pereira MS, et al. 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. 2006; 193(9):1313-22.
Hajjaran H, Mohebali M, Mamishi S, Vasigheh F, Oshaghi MA, Naddaf SR, Teimouri A, Edrissian GH, Zarei Z. Molecular identification and polymorphism determination of cutaneous and visceral leishmaniasis agents isolated from human and animal hosts in Iran. Biomed Res Int. 2013.Article ID 789326, 7 pages.
Ji J, Masterson J, Sun J, Soong L. CD4+ CD25+ Regulatory T Cells Restrain Pathogenic Responses during Leishmania amazonensis Infection. J Immunol. 2005; 174(11): 7147–53.
Rodrigues OR, Marques C, Soares-Clemente M, Ferronha MH, et al. Identification of regulatory T cells during experimental Leishmania infantum infection. 2008; 214(2):101-11.
Gupta G, Majumdar S, Adhikari A, Bhattacharya P, et al. Treatment with IP-10 induces host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice. Med Microbiol Immunol. 2011; 200(4):241-53.
Rai AK, Thakur CP, Singh A, Seth T, et al. Regulatory T cells suppress T cell activation at the pathologic site of human visceral leishmaniasis. PloS One. 2012; 7(2):e31551.
Hoseini Sh, Javanmard Sh, Sayyed Zarkesh H, Khamesipour A, et al. Regulatory T-cell profile in early and late lesions of cutaneous leishmaniasis due to Leishmania major. J Res Med Sci. 2012; 17(6): 513-8.
Rodriguez-Pinto D, Navas A, Blanco VM, Ramírez L, et al. Regulatory T cells in the pathogenesis and healing of chronic human dermal leishmaniasis caused by Leishmania (Viannia) species. PloS Negl Trop Dis. 2012; 6(4):e1627.
Costa DL, Guimarães LH, Cardoso TM, Queiroz A, et al. Characterization of regulatory T cell (Treg) function in patients infected with Leishmania braziliensis. Hum Immunol. 2013; 74(12):1491-1500.
Bahrami F, Darabi H, Riazi-Rad F, Khaze V, et al. FOXP3 expression and frequency of regulatory T cells in healed individuals from Leishmania major infection and the asymptomatic cases. Hum Immunol; 2014; 75(10):1026-33.
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