Individuals in an endemic region for Leishmania braziliensis display lower levels of CD45RO in T cells

Authors

DOI:

https://doi.org/10.33448/rsd-v11i5.28255

Keywords:

Flow cytometry; Leishmaniasis; Cutaneous; Neglected disease; T-Lymphocytes.

Abstract

Cutaneous Leishmaniasis (CL) is an important neglected tropical disease, that reaches about 900 thousand to 1.5 million people annually, mainly in Brazil.  The present study aimed to characterize these lymphocyte populations and the expression of the CD45RO marker profile in patients with CL. We evaluated CD4+, CD8+, double-positive (DP) and double-negative (DN) T cells and their expression of CD45RO in Cutaneous Leishmaniasis patients, divided into three groups: before treatment (BT), posttreatment (PT) and subclinical (SC). CD4+ T cells had a higher percentage in PT and SC groups when compared to the control group (CT). CD4+ T cells presented a greater expression of CD45RO in BT and PT groups compared to the SC group, that had a lower expression compared with the CT. CD8+ T lymphocytes had a higher percentage in BT when compared with CT and a greater expression of CD45RO when compared to PT, SC and CT groups. We did not observe any statistical significance in the percentage of the DP and DN lymphocytes, however, we noticed that the DP lymphocytes presented a lower expression of CD45RO in the SC group when compared to the CT group, whereas the DN lymphocytes showed a greater expression of CD45RO in the BT group when compared with the other groups. CD4+ T cells appear to be protective in these patients and CD8+ T lymphocytes seem to be associated to pathogenesis, while DP CD45RO+ and DN CD45RO+ lymphocytes appear to play a dual role.

Author Biographies

Marton Kaique de Andrade Cavalcante, Instituto Aggeu Magalhães; Universidade Federal de Pernambuco

Marton Kaique de Andrade Cavalcante graduated in Nursing from the Federal University of Pernambuco (UFPE), has a master's degree (2020) in Therapeutic Innovation from UFPE. He is currently doing a PhD in Therapeutic Innovation from UFPE. Since his scientific initiation, he has been working on the immune response in patients with cutaneous leishmaniasis.

Rafael de Freitas e Silva, Universidade de Pernambuco

Rafael de Freitas e Silva graduated in Biomedicine from the Federal University of Pernambuco (UFPE), has a master's degree in Nuclear Energetic Technologies from UFPE and a doctorate in Therapeutic Innovation from UFPE. Since 2012, He is Adjunct Professor of Immunology at University of Pernambuco (UPE).

Valéria Rêgo Alves Pereira, Instituto Aggeu Magalhães

Valéria Rêgo Alves Pereira has a PhD in Cellular and Molecular Biology from the Oswaldo Cruz Foundation (2003). Currently she is a Senior Technologist in Public Health and responsible for the Flow Cytometry Core unit at Aggeu Magalhães Institute (IAM/FIOCRUZ/PE). She is part of the Ethics Committee in Human Research of IAM and a professor on the Post-Graduation programs of Therapeutic Innovation (UFPE) and Health Biosciences and Biotechnology (IAM). She leads the research group of Immunology of Infectious and Parasitic Diseases, has expertise in Immunology with emphasis in Immunoparasitology, acting mainly on the studies of the cellular and humoral responses of individuals who are susceptible to infectious and parasitic diseases in different stages of the pathological process, mainly with leishmaniasis.

Maria Carolina Accioly Brelaz-de-Castro, Universidade Federal de Pernambuco

Maria Carolina Accioly Brelaz-de-Castro graduated in Biomedicine from the Federal University of Pernambuco (UFPE), has a master's degree in Sciences from the Aggeu Magalhães Institute (IAM) and a doctorate (2013) and post-doctorate (2015) in Therapeutic Innovation from UFPE. She is currently a professor at UFPE and at the postgraduate program in Therapeutic Innovation, from the same University. She is a collaborator of IAM and a member of their flow cytometry core unit. She has experience in the fields of Immunology and Parasitology and her research group is focused on the development of immunological biomarkers and vaccines for infectious and parasitic diseases, mainly working with leishmaniasis.

References

Antonelli, L. R. V., Dutra, W. O., Oliveira, R. R., Torres, K. C., Guimarães, L. H., Bacellar, O. & Gollob, K. J. (2006). Disparate Immunoregulatory Potentials for Double-Negative (CD4-CD8-) αβ and γδ T Cells from Human Patients with Cutaneous Leishmaniasis. Infection and Immunity, 74, 6317-6323.

Bittar, R. C., Nogueira, R. S., Vieira-Gonçalves, R., Pinho-Ribeiro, V., Mattos, M. S., Oliveira-Neto, M. P., Coutinho, S. G. & Da-Cruz, A. M. (2007). T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis. Mem Inst Oswaldo Cruz, 102, 625-630.

Brasil. Ministério da Saúde. (2021). Departamento de Informática do SUS. Brasil: DATASUS. http://datasus.saude.gov.br/

Brelaz-de-Castro, M. C. A., Almeida, A. F., Oliveira, A. P., Assis-Souza, M., Rocha, L. F. & Pereira, V. R. A. (2012) Cellular immune response evaluation of cutaneous leishmaniasis patients cells stimulated with Leishmania (Viannia) braziliensis antigenic fractions before and after clinical cure. Cellular Immunology, 279, 180-186.

Clarêncio, J., Oliveira, C. I., Favali, C., Medina, O., Caldas, A., Costa, C. H., Costa, D. L., Brodskyn, C., Barral, A. & Barral-Neto, M. (2008). Could the lower frequency of CD8+CD18+CD45RO+ lymphocytes be biomarkers of human VL? International Immunology, 21, 137-144.

Conceição-Silva, F., Perlaza, B. L., Louis, J. A. & Romero, P. (1994). Leishmania major infection in mice primes for specific major histocompatibility complex class I-restricted CD8+ cytotoxic T cell responses. European Journal of Immunology, 24, 2813-2917.

Cunha, C. F., Ferraz, R., Pimentel, M. I. F., Lyra, M. R., Schubach, A., Da-Cruz, A. M. & Bertho, A. L. (2016). Cytotoxic cell involvement in human cutaneous leishmaniasis: assessments in active disease, under therapy and after clinical cure. Parasite Immunology, 38, 244-254.

Da-Cruz, A. M., Conceição-Silva, F., Bertho, A. L. & Coutinho, S. G. (1994). Leishmania-Reactive CD4+ and CD8+ T Cells Associated with Cure of Human Cutaneous Leishmaniasis. Infection and Immunity, 62, 2614-2618.

Desfrançois, J., Derré, L., Corvaisier, M., Le Mével, B., Catros, V., Jotereau, F. & Gervois, N. (2009). Increased frequency of nonconventional double positive CD4CD8 alphabeta T cells in human breast pleural effusions. Int J Cancer, 125, 374-380.

Doyle, C. & Strominger, J. L. (1987). Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature, 330, 256-259.

Eljaafari, A., Yuruker, O., Ferrand, C., Farre, A., Addey, C., Tartelin, M. L., Thomas, X., Tiberghien, P., Simpson, E., Rigal, D. & Scott, D. (2013). Isolation of Human CD4/CD8 Souble-Positive, Graft-Versus-Host Disease-Protective, Minor Histocompatibility Antigen-Specific Regulatory T Cells and of a Novel HLA-DR7-Restricted HY-Specific CD4 Clone. The Journal of Immunology, 190, 184-194.

Ferraz, R., Cunha, C. F., Pimentel, M. I. F., Lyra, M. R., Pereira-da-Silva, T., Schubach, A. O., Da-Cruz, A. M. & Bertho, A. L. (2017). CD3+CD4negCD8neg (double negative) T lymphocytes and NKT cells as the main cytotoxic-related-CD107a+ cells in lesions of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis. Parasites & Vectors, 10, 1-12.

Fischer, K., Voelkl, S., Heymann, J., Przybylski, G. K., Mondal, K., Laumer, M., Kunz-Schughart, L., Schmidt, C. A., Andreesen, R. & Mackensen, A. (2005). Isolation and characterization of human antigen-specific TCR alpha beta+ CD4(-)CD8- double-negative regulatory T cells. Blood, 105, 2828-2835.

Follador, I., Araújo, C., Bacellar, O., Araújo, C. B., Carvalho, L. P., Almeida, R.P. & Carvalho, E. M. (2002). Epidemiologic and immunologic findings for the subclinical form of Leishmania braziliensis infection. Clin Infect Dis, 34, e54-e58.

Frahm, M. A., Picking, R. A., Kurucs, J. A., McGee, K. S., Gay, C. L., Eron, J. J., Hicks, C. B., Tomaras, G. D. & Ferrari, G. (2012). CD4+CD8+ T-cells Represent a Significant Portion of the Anti-HIV T-cell Response to Acute HIV Infection. J Immunol, 188, 4289-4296.

Gollob, K. J., Antonelli, L. R. V., Faria, D. R., Keesen, T. S. L. & Dutra, W. O. (2008). Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology. Int Immunopharmacol, 8, 1338-1343.

Heinzel, F. P., Schoenhaut, D. S., Rerko, R. M., Rosser, L. E. & Gately, L. E. (1993). Recombinant interleukin 12 cures mice infected with Leishmania major. Journal of Experimental Medicine, 177, 1505-1509.

Iwatani, Y., Hidaka, Y., Matsuzuka, F., Kuma, K. & Amino, N. (1993). Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease. Clin Exp Immunol, 93, 430-436.

Koh, C. C., Wardini, A. B., Vieira, M., Passos, L. S. A., Martinelli, P. M., Neves, E. G. A., Antonelli, L. R. V., Barbosa, D. F., Velikkakam, T., Gutseit, E., Menezes, G. B., Giunchetti, E., Machado, P. R. L., Carvalho, E. M., Gollob, K. J. & Dutra, W. O. (2020). Human CD8+ T Cells Release Extracellular Traps Co-Localized with Cytotoxic Vesicles That Are Associated With Lesion Progression and Severity in Human Leishmaniasis. Front Immunol, 1, 1-19.

Liew, F. Y., Millott, S., Parkinson, C., Palmer, R. M. & Moncada, S. (1990). Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol, 144, 4794-4797.

Martinez-Arends, A., Tapia, F. J., Cáceres-Dittmar, G., Mosca, W., Valecillos, L. & Convit, J. (1991). Immunocytochemical characterization of immune cells in lesions of American cutaneous leishmaniasis using novel T cell markers. Acta Tropica, 49, 271-280.

Mendes-Aguiar, C. O., Vieira-Gonçalves, R., Guimarães, L. H., Oliveira-Neto, M. P., Carvalho, E. M. & Da-Cruz, A. M. (2016). Effector memory CD4+ T cells differentially express activation associated molecules depending on the duration of American cutaneous leishmaniasis lesions. Clinical & Experimental Immunology, 185, 202-209.

Muniz, A. C., Bacellar, O., Lago, E. L., Carvalho, A. M., Carneiro, P. P., Guimarães, L. H., Rocha, P. N., Carvalho, L. P., Glesby, M. & Carvalho, E. M. (2016). Immunologic Markers of Protection in Leishmania (Viannia) braziliensis Infection: A 5-yeas Cohort Study. The Journal of Infectious Diseases, 214, 570-576.

Murphy, K., Travers, P. & Walport, M. (2014). Imunologia de Janeway. (8th ed). Artmed.

Murray, H. W. (1981). Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages. Journal of Experimental Medicine, 153, 1302-1315.

Nascimbeni, M., Shin, E., Chiriboga, L., Kleiner, D. E. & Rehermann, B. (2004). Peripheral CD4+CD8+ T cells are differentiated effector memory cells with antiviral functions. Immunobiology, 104, 478-486.

Novais, F. O., Carvalho, L. P., Graff, J. W., Beiting, D. P., Ruthel, G., Roos, D. S., Betts, M. R., Goldschmidt, M. H., Wilson, M. E., Oliveira, C. I. & Scott, P. (2013). Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis. PLoS Pathog, 9, 1-11.

Novais, F. O., Wong, A. C., Villareal, D. O., Beiting, D. P. & Scott P. (2018). CD8+ T Cells Lack Local Signals To Produce IFN-γ in the Skin during Leishmania Infection. J Immunol, 200, 1737-1745.

Organización Panamericana de la Salud. (2019). Manual de procedimientos para vigilancia y control de las leishmaniasis en las Américas. (1a ed.), Washington, DC: OPAS.

Overgaard, N. H., Jung, J. W., Steptoe, R. J. & Weels, J. W. (2015). CD4+/CD8+ double-positive T cells: more than just a developmental stage? Journal of Leujocyte Biology, 97, 31-38.

Santos, C. S., Boaventura, V., Cardoso, C. R., Tavares, N., Lordelo, M. J., Noronha, A., Costa, J., Borges, V. M., Oliveira, C. I., Weyenbergh, J. V., Barral, A., Barral-Neto, M. & Brodskyn, C. I. (2013). CD8(+) Granzyme B(+)-mediated tissue injury versus CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis. J Invest Dermatol, 33, 1533–40.

Silva, R. F., Oliveira, B. C., Silva, A. A., Castro, M. C. A. B., Ferreira, L. F. G. R., Hernandes, M. Z., Brito, M. E. F., de-Melo-Neto, O. P., Brito, M. E. F., de-Melo-Neto, O. P., Rezende, A. M. & Pereira, V. R. A. (2019). Immunogenicity of Potential CD4+ and CD8+ T Cell Epitopes Derived from the Proteome of Leishmania braziliensis. Front Immunol, 3145, 1-14.

Scott, P., Natovitz, P., Coffman, R. L., Pearce, E. & Sher, A. (1988). Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. Journal of Experimental Medicine, 168, 1675-1684.

World Health Organization. (2021). Leishmaniasis. WHO.

Zuckermann, F. A. & Husmann, R. J. (1996). Functional and phenotypic analysis of porcine peripheral blood CD4/CD8 double-positive T cells. Immunology, 87, 500-512.

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Published

04/04/2022

How to Cite

CAVALCANTE, M. K. de A. .; REHN, V. N. C. .; BRITO, M. E. F. de .; SILVA, R. de F. e .; PEREIRA, V. R. A. .; BRELAZ-DE-CASTRO, M. C. A. . Individuals in an endemic region for Leishmania braziliensis display lower levels of CD45RO in T cells. Research, Society and Development, [S. l.], v. 11, n. 5, p. e22811528255, 2022. DOI: 10.33448/rsd-v11i5.28255. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/28255. Acesso em: 26 apr. 2024.

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Health Sciences