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'T IND.REG' depletion by anti-CD25 (PC61) MAb treatment does not change parasitaemia levels or acute phase tissue pathology in mice infected with Trypanosoma cruzi

F D Pretel C A Zago; S M Muxel; L R Sardinha; D Z Bucci; Maria Regina D'Império Lima; José Maria Alvarez; Meeting of the Brazilian Society for Immunology (31. 2006 Búzios)

Abstracts São Paulo, SP: Brazilian Society for Immunology, 2006

São Paulo 2006

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  • Título:
    'T IND.REG' depletion by anti-CD25 (PC61) MAb treatment does not change parasitaemia levels or acute phase tissue pathology in mice infected with Trypanosoma cruzi
  • Autor: F D Pretel
  • C A Zago; S M Muxel; L R Sardinha; D Z Bucci; Maria Regina D'Império Lima; José Maria Alvarez; Meeting of the Brazilian Society for Immunology (31. 2006 Búzios)
  • Assuntos: IMUNOLOGIA
  • É parte de: Abstracts São Paulo, SP: Brazilian Society for Immunology, 2006
  • Notas: Disponível em CD-ROM
  • Descrição: Introduction and Objectives: T regulatory cells (TREG; CD4+CD25+FoxP3+) are involved in the control of immune responses to autoantigens and exogenous antigens. In vivo treatment with MAb specific for the IL-2R alpha chain (anti-CD25; clones PC61 or 7D4) is widely used to deplete TREG cells. In this work, we analyzed the effects of PC61MAb pretreatment in the evolution of the acute infection by T. cruzi. Material & Methods: C57BL/6 mice were treated with three 1 mg doses, two days apart, of PC61 (anti-CD25) or GL113 (isotypic control) MAb. Three days after the last dose mice were either sacrificed for TREG depletion evaluation, or infected with 103 T. cruzi parasites (Y strain). Infected mice were screened daily for parasitaemias and killed at day 13 p.i. for phenotypic analysis and histopathology. Results and Conclusion: In non-infected mice, treatment with PC61 resulted in 80% reduction in the number of CD25+CD4+ T cells (estimated by 7D4 staining), but just in 30% reduction in the number of FoxP3+CD4+ T cells, suggesting that in PC61-treated mice part of the TREG population persists with down-modulated CD25 expression. Importantly, the spleen of PC61-treated mice contained a higher number of CD4+ cell blasts than untreated mice. Similarly, the infection-induced increase in the frequency of CD4+ cell blasts was more intense in PC61- than in GL113-treated mice. Infected mice showed a strong raise in the number of CD4+CD25+ cells and,
    paradoxically, the raise was higher in PC61-treated mice. More important, in relation to untreated non-infected mice, both PC61-treated or GL113-treated infected mice displayed an important enhance in the numbers of CD4+CD25+Foxp3+ cells (4,7 and 3,0 fold, respectively) and CD4+CD25-Foxp3+ (3,2 and 3,1 fold). Parasitaemias did not differed between PC61- and GL113-treated infected groups. Moreover, no differences were observed between these groups, at day 13 p.i., in terms of heart pathology. Our results indicate that partial TREG cell depletion does not alter the acute T. cruzi infection. More importantly, spleen cells displaying TREG markers increase in response to infection, an increase not affected by pretreatment with anti-CD25 MAb.
  • Editor: São Paulo
  • Data de criação/publicação: 2006
  • Formato: res. CI.046.
  • Idioma: Inglês

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