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 rMSp139 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.
Lingua originale | English |
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pagine (da-a) | 222-235 |
Numero di pagine | 14 |
Rivista | Journal of Immunology |
Volume | 2010 |
DOI | |
Stato di pubblicazione | Pubblicato - 2010 |
Keywords
- CD8
- Experimental Autoimmune Encephalomyelitis
- Mycobacterium smegmatis