| Author | Geluk, Annemieke | |
| Author | van den Eeden, Susan J. F. | |
| Author | Dijkman, Karin | |
| Author | Wilson, Louis | |
| Author | Kim, Hee Jin | |
| Author | Franken, Kees L. M. C. | |
| Author | Spencer, John S. | |
| Author | Pessolani, Maria C. V. | |
| Author | Pereira, Geraldo M. B. | |
| Author | Ottenhoff, Tom H. M. | |
| Access date | 2018-04-26T12:40:05Z | |
| Available date | 2018-04-26T12:40:05Z | |
| Document date | 2011 | |
| Citation | GELUK, Annemieke; et al. ML1419c peptide-immunization induces Mycobacterium lepraespecific HLA-A*0201-restricted CTL in vivo with potential to kill live mycobacteria1. J Immunol., v.187, n.3, p.1393-1402, Aug. 2011. | pt_BR |
| ISSN | 0022-1767 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/26123 | |
| Language | eng | pt_BR |
| Publisher | American Association of Immunologists | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Mycobacterium leprae | pt_BR |
| Subject in Portuguese | Diagnóstico | pt_BR |
| Subject in Portuguese | Linfócitos T CD8-Positivos | pt_BR |
| Subject in Portuguese | Antígenos HLA-A | pt_BR |
| Subject in Portuguese | citotoxicidade in vivo | pt_BR |
| Subject in Portuguese | Vacinas | pt_BR |
| Title | ML1419c peptide immunization induces Mycobacterium leprae-specific HLA-A*0201-restricted CTL in vivo with potential to kill live mycobacteria 1 | pt_BR |
| Type | Article | |
| DOI | 10.4049/jimmunol.1100980 | |
| Abstract | MHC class I-restricted CD8(+) T cells play an important role in protective immunity against mycobacteria. Previously, we showed that p113-121, derived from Mycobacterium leprae protein ML1419c, induced significant IFN-γ production by CD8(+) T cells in 90% of paucibacillary leprosy patients and in 80% of multibacillary patients' contacts, demonstrating induction of M. leprae-specific CD8(+) T cell immunity. In this work, we studied the in vivo role and functional profile of ML1419c p113-121-induced T cells in HLA-A*0201 transgenic mice. Immunization with 9mer or 30mer covering the p113-121 sequence combined with TLR9 agonist CpG induced HLA-A*0201-restricted, M. leprae-specific CD8(+) T cells as visualized by p113-121/HLA-A*0201 tetramers. Most CD8(+) T cells produced IFN-γ, but distinct IFN-γ(+)/TNF-α(+) populations were detected simultaneously with significant secretion of CXCL10/IFN-γ-induced protein 10, CXCL9/MIG, and VEGF. Strikingly, peptide immunization also induced high ML1419c-specific IgG levels, strongly suggesting that peptide-specific CD8(+) T cells provide help to B cells in vivo, as CD4(+) T cells were undetectable. An additional important characteristic of p113-121-specific CD8(+) T cells was their capacity for in vivo killing of p113-121-labeled, HLA-A*0201(+) splenocytes. The cytotoxic function of p113-121/HLA-A*0201-specific CD8(+) T cells extended into direct killing of splenocytes infected with live Mycobacterium smegmatis expressing ML1419c: both 9mer and 30mer induced CD8(+) T cells that reduced the number of ML1419c-expressing mycobacteria by 95%, whereas no reduction occurred using wild-type M. smegmatis. These data, combined with previous observations in Brazilian cohorts, show that ML1419c p113-121 induces potent CD8(+) T cells that provide protective immunity against M. leprae and B cell help for induction of specific IgG, suggesting its potential use in diagnostics and as a subunit (vaccine) for M. leprae infection. | pt_BR |
| Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
| Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
| Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
| Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
| Affilliation | Colorado State University. Department of Microbiology, Immunology, and Pathology. Fort Collins, CO, USA. | pt_BR |
| Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
| Affilliation | Colorado State University. Department of Microbiology, Immunology, and Pathology. Fort Collins, CO, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil / Universidade do Estado do Rio de Janeiro. Escola de Ciências Médicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Leiden University Medical Center. Department of Infectious Diseases. Leiden, Netherlands. | pt_BR |
| Subject | Mycobacterium leprae | pt_BR |
| Subject | diagnostics | pt_BR |
| Subject | vaccines | pt_BR |
| Subject | in vivo cytotoxicity | pt_BR |
| Subject | CD8+ T-cells | pt_BR |
| Subject | HLA-A*0201 | pt_BR |
| e-ISSN | 1550-6606 | |
| Embargo date | 2030-01-01 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
