Mycobacterium smegmatis expressing a chimeric protein MPT64-Proteolipid Protein (PLP) 139-151 reorganizes the PLP-specific T cell repertoire favoring a CD8-mediated response and induces a relapsing experimental autoimmune encephalomyelitis

Chiara Nicolò, Michela Sali, Gabriele Di Sante, Maria Concetta Geloso, Emanuela Signori, Romina Penitente, Shashi Uniyal, Monica Rinaldi, Loredana Ingrosso, Vito Michele Fazio, Bosco M C Chan, Giovanni Delogu, Francesco Ria

Research output: Contribution to journalArticle

Abstract

We infected SJL mice with a recombinant Mycobacterium smegmatis expressing a chimeric protein containing the self-epitope of proteolipid protein 139-151 (p139) fused to MPT64, a secreted protein of Mycobacterium tuberculosis (rMSp139). Infected mice developed a relapsing experimental autoimmune encephalomyelitis (EAE), showing a prevailing demyelination of the CNS, and disease severity was significantly lower in comparison with the one that follows immunization with p139. rMSp139 was not detected in lymph node or spleen in the course of clinical disease development or in the CNS during relapse. Infection with rMSp139 modified the p139-specific T cell repertoire, recruiting the spontaneous p139-specific repertoire and activating CD4+ T cells carrying the BV4 semiprivate rearrangement. T cells carrying the public BV10 rearrangement that are consistently found in the CNS during flares of disease were not activated by infection with rMS p139 because lymph node APCs infected with rMSp139 selectively fail to present the epitope for which BV10 cells are specific. Simultaneously, rMSp139 expanded p139-specific CD8+ cells more efficiently than immunization with peptide in adjuvant. SJL mice vaccinated against the CDR3 sequence of the BV10 public rearrangement reduced usage of the BV10 cells and displayed reduced symptoms during bouts of EAE. Thus, transient peripheral infection with a CNS-cross - reactive nonpathogenic Mycobacterium induces a relapsing EAE that continues long after clearance of the infectious agent. The composition of the self-reactive repertoire activated determines severity and histology of the resulting disease.

Original languageEnglish
Pages (from-to)222-235
Number of pages14
JournalJournal of Immunology
Volume184
Issue number1
DOIs
Publication statusPublished - Jan 1 2010

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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