nach oben

Erschienen in:

01.11.2014 | Original Research

Increase in the Expression of CD4 + CD25+ Lymphocytic T Cells in the Indeterminate Clinical Form of Human Chagas Disease After Stimulation With Recombinant Antigens of Trypanosoma cruzi

verfasst von: Suellen Carvalho de Moura Braz, Adriene Siqueira de Melo, Maria da Glória Aureliano de Melo Cavalcanti, Sílvia Marinho Martins, Wilson de Oliveira Jr, Edimilson Domingos da Silva, Antonio Gomes Pinto Ferreira, Virginia Maria Barros de Lorena, Yara de Miranda Gomes

Erschienen in: Journal of Clinical Immunology | Ausgabe 8/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Regulatory T cells are involved in the clinical course of chronic Chagas disease, possibly because they exercise a control in the patient’s inflammatory response to Trypanosoma cruzi. This study analyzed the levels of CD4 + CD25+ T cells in chronic Chagas disease patients after in vitro stimulation of the peripheral blood mononuclear cells with CRA (Cytoplasmic Repetitive Antigen) or FRA (Flagellar Repetitive Antigen) T. cruzi antigens.

Methods

Groups of patients with the cardiac form and indeterminate form; and non-infected individuals, were selected. The CD4 + CD25+ T lymphocyte population, as well as the FoxP3 expression and the IL10 production, were evaluated by flow cytometry after stimulation with CRA or FRA.

Result

The IND group presented higher levels of CD4 + CD25+ T cells than the CARD group. However, there was no evidence of a relationship between FoxP3 and IL10 with any of the chronic forms.

Conclusions

Our results suggest the possible involvement of CD4 + CD25+ T cells specific to CRA and FRA in controlling the progression of clinical outcomes. Though, further studies are needed to define which mechanisms activate regulatory T cells and lead to pathology control in chronic human Chagas disease.

Rassi Júnior A, Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010;375:1388–402.CrossRef

Albareda MC, Laucella SA, Alvarez MG, Armenti AH, Bertochi G, Tarleton RL, et al. Trypanosoma cruzi modulates the profile of memory CD8 T cells in chronic Chagas’ disease patients. Int Immunol. 2006;18:465–71.PubMedCrossRef

Albareda MC, Olivera GC, Laucella AS, et al. Chronic human infection with Trypanosoma cruzi drives CD4+ T cells to immune senescence. J Immunol. 2009;183:4103–8.PubMedCentralPubMedCrossRef

Bahia-Oliveira LMG, Gomes JAS, Rocha MOC, et al. IFN-γ in human Chagas’ disease: protection or pathology? Braz J Med Biol Res. 1998;31:127–31.PubMedCrossRef

Barros-Mazon S, Guariento ME, Silva CA, Coffman RL, Abrahamsohn IA. Differential regulation of lymphoproliferative responses to Trypanosoma cruzi antigen in patients with the cardiac or indeterminate form of Chagas disease. Clin Immunol. 2004;111:137–45.PubMedCrossRef

Cardoso GM, Morato MJ, Gomes JA, et al. Comparative analysis of cell phenotypes in different severe clinical forms of Chagas’ disease. Front Biosci. 2006;11:1158–63.PubMedCrossRef

Gomes JAS, Bahia-Oliveira LMG, Rocha MOC, Martins-Filho OA, Gazzinelli G, Correa-Oliveira R. Evidence that development of severe cardiomyophathy in human Chagas’ disease is due to a Th1-specific immune response. Infect Immun. 2003;71:1185–93.PubMedCentralPubMedCrossRef

Lorena VMB, Lorena IMB, Braz SCM, et al. Cytokine levels in serious cardiopathy of Chagas disease after in vitro stimulation with recombinant antigens from Trypanosoma cruzi. Scand J Immunol. 2010;72:529–39.PubMedCrossRef

Menezes CAS, Rocha MOC, Souza PEA, Chaves ACL, Gollob KJ, Dutra WO. Phenotypic and functional characteristics of CD28+ and CD28- cells from chagasic patients: distinct repertoire and cytokine expression. Clin Exp Immunol. 2004;137:129–38.PubMedCentralPubMedCrossRef

10.

Silveira ABM, Araújo FF, Freitas MAR, et al. Characterization of the presence and distribution of Foxp3⁺ cells in chagasic patients with and without megacolon. Hum Immunol. 2009;70:65–7.PubMedCrossRef

11.

Vitelli-Avelar DM, Sathler-Avelar R, Dias JCP, et al. Chagasic patients with indeterminate clinical form of the disease have high frequencies of circulating CD3⁺CD16⁻CD56⁺ natural killer T cells and CD4⁺CD25^High regulatory T lymphocytes. Scand J Immunol. 2005;62:297–308.PubMedCrossRef

12.

Vitelli-Avelar DM, Sathler-Avelar R, Massara RL, et al. Are increased frequency of macrophage-like and natural killer (NK) cells, together with high levels of NKT and CD4 + CD25high T cells balancing activated CD8+ T cells, the key to control Chagas’ disease morbidity? Clin Exp Immunol. 2006;145:81–92.PubMedCentralPubMedCrossRef

13.

Vitelli-Avelar DM, Sathler-Avelar R, Teixeira-Carvalho A, Dias JCP, Gontijo ED, Faria AM, et al. Strategy to asses the overall cytokine profile of circulating leukocytes and its association with distinct clinical forms of human Chagas disease. Scand J Immunol. 2008;68:516–25.PubMedCrossRef

14.

Jiang H, Chess LB. An integrated view of suppressor T cell subsets in immunoregulation. J Clin Invest. 2004;114:1198–208.PubMedCentralPubMedCrossRef

15.

Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat Immunol. 2005;6:353–60.PubMedCrossRef

16.

Cederbom L, Hall H, Ivars F. CD4 + CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur J Immunol. 2000;6:1538–43.CrossRef

17.

Fehérvari Z, Sakaguchi S. CD4⁺ Tregs and immune control. J Clin Invest. 2004;114:1209–17.PubMedCentralPubMedCrossRef

18.

Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). J Immunol. 1995;155:1151–64.PubMed

19.

Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.PubMedCrossRef

20.

Belkaid Y, Sun CM, Bouladoux N. Parasites and immunoregulatory T cells. Curr Opin Immunol. 2006;18:406–12.PubMedCrossRef

21.

Gutierrez FRS, Guedes PMM, Gazzinelli RT, Silva JS. The role of parasite persistence in pathogenesis of Chagas heart disease. Parasite Immunol. 2009;31:673–85.PubMedCrossRef

22.

Miyara M, Sakaguchi S. Natural regulatoryT cells: mechanisms of suppression. Trends Mol Med. 2007;13:108–16.PubMedCrossRef

23.

Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol. 2003;4:330–6.PubMedCrossRef

24.

Zirgler SF. FOXP3: of mice and men. Annu Rev Immunol. 2006;24:209–26.CrossRef

25.

Araújo FF, Gomes JA, Rocha MO, Williams-Blangero S, Pinheiro VM, Morato MJ, et al. Potencial role of CD4⁺CD25^high regulatory T cells in morbidity in Chagas disease. Front Biosci. 2007;12:2797–806.PubMedCrossRef

26.

Araújo FF, Vitelli-Avelar DM, Teixeira-Carvalho A, et al. Regulatory T cells phenotype in different clinical forms of Chagas’ disease. PLoS Negl Trop. 2011;5:e992.CrossRef

27.

Araújo FF, Corrêa-Oliveira R, Rocha MOC, et al. Foxp3⁺CD25^high CD4⁺ regulatory T cells from indeterminate patients with Chagas disease can suppress the effector cells and cytokines and reveal altered correlations with disease severity. Immunobiology. 2012;217:768–77.PubMedCrossRef

28.

Kotner J, Tarleton R. Endogenous CD4⁺CD25⁺ regulatory T cells have a limited role in the control of Trypanosoma cruzi in mice. Infect Immun. 2007;75:861–9.PubMedCentralPubMedCrossRef

29.

Guedes PMM, Gutierrez FRS, Silva GK, et al. Deficient regulatory T cell activity and Low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas’ disease. PLoS Negl Trop Dis. 2012;6:e1630.PubMedCentralPubMedCrossRef

30.

Araujo FG. Analysis of Trypanosoma cruzi antigens bound by specific antibodies and by antibodies to related Trypanosomatids. Infect Immun. 1986;53:179–85.PubMedCentralPubMed

31.

Malchiodi EL, Chiaramontb MG, Taranto NJ, Zwirner NW, Margni RA. Cross-reactivity studies and differential serodiagnosis of human infections caused by Trypanosoma cruzi and Leishmania spp; use of immunoblotting and ELISA with a purified antigen (Agl63B6). Clin Exp Immunol. 1994;97:417–23.PubMedCentralPubMedCrossRef

32.

Lafaille JJ, Linss J, Krieger MA, Souto-Padrón T, Wanderley S, Goldenberg S. Structure and expression of two Trypanosoma cruzi genes encoding antigenic proteins bearing repetitive epitopes. Mol Biochem Parasitol. 1989;35:127–36.PubMedCrossRef

33.

Krieger MA, Almeida E, Oelemann W, Lafaille JJ, Pereira JB, Krieger H, et al. Use of recombinant antigens for the accurate immunodiagnosis of Chagas’disease. Am J Trop Med Hyg. 1992;46:427–34.PubMed

34.

Ibañez CF, Affranchino JL, Macina RA, et al. Multiple Trypanosoma cruzi antigens containing tandemly repeated amino acid sequence motifs. Mol Biochem Parasitol. 1988;30:27–34.PubMedCrossRef

35.

Vasconcelos RHT, Amaral FN, Cavalcanti MGAM, Silva ED, Ferreira AGP, Morais CNL, et al. Increased levels of IgA antibodies against CRA and FRA recombinant antigens of Trypanosoma cruzi differentiate digestive forms of Chagas disease. Hum Immunol. 2010;71:964–7.PubMedCrossRef

36.

Verçosa AFA, Lorena VMB, Carvalho CL, et al. Chagas’ disease: IgG isotypes against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens of Trypanosoma cruzi in chronic Chagasic patients. J Clin Lab Anal. 2007;21:271–6.PubMedCrossRef

37.

Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in chocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol. 1976;37:7–11.PubMedCrossRef

38.

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–5.PubMedCrossRef

39.

Morrissey JH. Silver stain for proteins in poliacrylamide gel: a modified procedure with enhanced uniform sensitivity. Anal Biochem. 1981;117:307–10.PubMedCrossRef

40.

Lorena VMB, Verçosa AFA, Machado RCA, et al. Cellular immune response from chagasic patients to CRA or FRA recombinant antigens of Trypanosoma cruzi. J Clin Lab Anal. 2008;22:91–8.PubMedCrossRef

41.

Braz SCM, Lorena VMB, Melo AS, Cavalcanti MGAM, Gomes YM. Evaluation of CD4 + CD25+ T lymphocyte response time kinetics in patients with chronic Chagas disease after in vitro stimulation with recombinant Trypanosoma cruzi antigens. Rev Soc Bras Med Trop. 2013;46:362–6.PubMedCrossRef

42.

Hudson TH, Grillo FG. Brefeldin-A enhancement of ricin A-chain Immunotoxins and blockade of intact ricin, Modeccin, and Abri. J Biol Chem. 1991;266:18586–92.PubMed

43.

Mariano FS, Gutierrez FRS, Pavanelli WR, et al. The involvement of CD4 + CD25+ T cells in the acute phase of Trypanosoma cruzi infection. Microbes Infect. 2008;10:825–33.PubMedCrossRef

44.

Sales-Júnior PA, Golgher D, Oliveira RV, Vieira V, Arantes RME, Lannes-Vieira J, et al. The regulatory CD4 + CD25+ T cells have a limited role on pathogenesis of infection with Trypanosoma cruzi. Microbes Infect. 2008;10:680–8.CrossRef

45.

Araújo FF, Silveira ABM, Corrêa-Oliveira R, Adad SJ, Fiuza JA. Characterization of the presence of Foxp3+ T cells from patients with different clinical forms of Chagas’ disease. Hum Immunol. 2011;42:299–302.

46.

Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA. CD4 + CD25high regulatory cells in human peripheral blood. J Immunol. 2001;167:1245–53.PubMedCrossRef

47.

Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol. 2003;3:253–7.PubMedCrossRef

48.

Sakaguchi S, Miyara M, Constantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010;10:490–500.PubMedCrossRef

49.

Sakaguchi S. Naturally arising CD4⁺ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531–62.PubMedCrossRef

50.

Teixeira MM, Gazzinelli RT, Silva JS. Chemokines, inflammation and Trypanosoma cruzi infection. Trends Parasitol. 2002;18:262–5.PubMedCrossRef

51.

Oliveira GM, Diniz RL, Batista W, Batista MM, Correa CB, Arauji-Jorge TC, et al. Fas ligand-dependent inflammatory regulation in acute myocarditis induced by Trypanosoma cruzi infection. Am J Pathol. 2007;17:79–86.CrossRef

52.

Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4⁺CD25⁺Foxp3⁺ regulatory T cells induce cytokine deprivation–mediated apoptosis of effector CD4⁺ T cells. Nat Immunol. 2007;8:1353–62.PubMedCrossRef

53.

Grossman WJ, Verbsky JW, Tollefsen BL, Kemper C, Atkinson JP, Ley TJ. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood. 2004;104:2840–8.PubMedCrossRef

54.

Strauss L, Bergmann C, Whiteside TL. Human circulating CD4⁺CD25^highFoxp3⁺ regulatory T cells kill autologous CD8⁺ but not CD4⁺ responder cells by Fas-mediated apoptosis. J Immunol. 2009;182:1469–80.PubMedCentralPubMedCrossRef

Titel: Increase in the Expression of CD4 + CD25+ Lymphocytic T Cells in the Indeterminate Clinical Form of Human Chagas Disease After Stimulation With Recombinant Antigens of Trypanosoma cruzi
verfasst von: Suellen Carvalho de Moura Braz
Adriene Siqueira de Melo
Maria da Glória Aureliano de Melo Cavalcanti
Sílvia Marinho Martins
Wilson de Oliveira Jr
Edimilson Domingos da Silva
Antonio Gomes Pinto Ferreira
Virginia Maria Barros de Lorena
Yara de Miranda Gomes
Publikationsdatum: 01.11.2014
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 8/2014
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-014-0092-6

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Increase in the Expression of CD4 + CD25+ Lymphocytic T Cells in the Indeterminate Clinical Form of Human Chagas Disease After Stimulation With Recombinant Antigens of Trypanosoma cruzi

Abstract

Purpose

Methods

Result

Conclusions

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin

Springer Medizin

Abstract

Purpose

Methods

Result

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2014

The First US Domestic Report of Disseminated Mycobacterium avium Complex and Anti-Interferon-γ Autoantibodies

Polyfunctional Analysis of Human Cytomegalovirus (HCMV)-Specific CD4+ and CD8+ Memory T-Cells in HCMV-Seropositive Healthy Subjects Following Different Stimuli

Prevalence and Morbidity of Primary Immunodeficiency Diseases, United States 2001–2007

Combined Immunodeficiency Evolving into Predominant CD4+ Lymphopenia Caused by Somatic Chimerism in JAK3

Immunodeficiency Associated with a Nonsense Mutation of IKBKB

Interleukin-2-Inducible T-Cell Kinase (ITK) Deficiency - Clinical and Molecular Aspects

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin