In:
The Journal of Immunology, The American Association of Immunologists, Vol. 187, No. 3 ( 2011-08-01), p. 1393-1402
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1100980
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2011
ZDB Id:
1475085-5
