We infected SJL mice with a recombinant M. smegmatis expressing a chimeric protein containing the self-epitope of proteolipid protein (PLP) 139-151 (p139) fused to MPT64, a secreted protein of M. tb (rMS p139). Infected mice developed a relapsing EAE showing a prevailing demyelination of the CNS and disease severity was significantly lower in comparison to the one that follows immunization with p139. rMS p139 was not detected in LN 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 rMSp139 since lymph node APC infected with rMS p139 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 non-pathogenic 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.

Nicolo', C., Sali, M., Di Sante, G., Geloso, M. C., Penitente, R., Delogu, G., Ria, F., Mycobacterium smegmatis expressing a chimeric protein MPT64-PLP139-151 reorganizes the PLP-specific T cell repertoire favouring a CD8-mediated response and induces a relapsing EAE1., <<JOURNAL OF IMMUNOLOGY>>, 2010; 184 (1): 222-235 [http://hdl.handle.net/10807/31316]

Mycobacterium smegmatis expressing a chimeric protein MPT64-PLP139-151 reorganizes the PLP-specific T cell repertoire favouring a CD8-mediated response and induces a relapsing EAE1.

Nicolo', Chiara;Sali, Michela;Di Sante, Gabriele;Geloso, Maria Concetta;Penitente, Romina;Delogu, Giovanni;Ria, Francesco
2010

Abstract

We infected SJL mice with a recombinant M. smegmatis expressing a chimeric protein containing the self-epitope of proteolipid protein (PLP) 139-151 (p139) fused to MPT64, a secreted protein of M. tb (rMS p139). Infected mice developed a relapsing EAE showing a prevailing demyelination of the CNS and disease severity was significantly lower in comparison to the one that follows immunization with p139. rMS p139 was not detected in LN 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 rMSp139 since lymph node APC infected with rMS p139 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 non-pathogenic 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.
Inglese
Nicolo', C., Sali, M., Di Sante, G., Geloso, M. C., Penitente, R., Delogu, G., Ria, F., Mycobacterium smegmatis expressing a chimeric protein MPT64-PLP139-151 reorganizes the PLP-specific T cell repertoire favouring a CD8-mediated response and induces a relapsing EAE1., <<JOURNAL OF IMMUNOLOGY>>, 2010; 184 (1): 222-235 [http://hdl.handle.net/10807/31316]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/31316
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