title: 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.
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 (rMS(p139)). 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. rMS(p139) was not detected in lymph node or spleen in the course of clinical disease development or in the CNS during relapse. Infection with rMS(p139) 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 rMS(p139) selectively fail to present the epitope for which BV10 cells are specific. Simultaneously, rMS(p139) 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.
authors: Institute of General Pathology, Catholic University, Rome, Italy.
authors: Chiara
authors: C
authors: Nicolò
authors: Michela
authors: M
authors: Sali
authors: Gabriele
authors: G
authors: Di Sante
authors: Maria Concetta
authors: MC
authors: Geloso
authors: Emanuela
authors: E
authors: Signori
authors: Romina
authors: R
authors: Penitente
authors: Shashi
authors: S
authors: Uniyal
authors: Monica
authors: M
authors: Rinaldi
authors: Loredana
authors: L
authors: Ingrosso
authors: Vito Michele
authors: VM
authors: Fazio
authors: Bosco M C
authors: BM
authors: Chan
authors: Giovanni
authors: G
authors: Delogu
authors: Francesco
authors: F
authors: Ria
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D020102:Mycobacterium smegmatis / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080865:MPB64 protein, Mycobacterium; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C435023:myelin proteolipid protein (139-151)