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International Immunology Advance Access originally published online on January 13, 2006
International Immunology 2006 18(2):363-374; doi:10.1093/intimm/dxh376
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Mycobacterium tuberculosis in the adjuvant modulates the balance of Th immune response to self-antigen of the CNS without influencing a "core" repertoire of specific T cells

Chiara Nicolò1, Gabriele Di Sante1, Massimiliano Orsini2, Simona Rolla1,3, Sandra Columba-Cabezas4, Vincenzo Romano Spica2,5, Gualtiero Ricciardi2, Bosco Man Chu Chan6 and Francesco Ria1

1 Institute of General Pathology and 2 Institute of Hygiene, Catholic University, L.go F. Vito 1, 00168 Rome, Italy
3 Department of Clinical and Biological Sciences, Ospedale S. L. Gonzaga, University of Turin, 10043 Orbassano, Torino, Italy
4 Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy
5 University of Movement Sciences (IUSM), P.zza L. De Bosis 6, 00194 Rome Italy
6 Biotherapeutics Research Group, Robarts Research Institute and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

Correspondence to: F. Ria; E-mail: fria{at}rm.unicatt.it

In the present study, we use modified CDR3 beta-chain spectratyping (immunoscope) to dissect the effect of Mycobacterium tuberculosis (MT)-derived proteins on individual PLP139-151-specific cells in the SJL mouse strain. In this model, the immunoscope technique allows the characterization of a public TCR that involves rearrangement of Vbeta10 and Jbeta1.1 and a semi-private TCR characterized by rearrangement of Vbeta4 and Jbeta1.6. Both rearrangements are specific for PLP139-151 and sequences of the CDR3 region of the two beta-chains show a conserved motif for the public rearrangement and related but more variable sequences for the semi-private rearrangement. MT-derived proteins promote increase of IFN-gamma-secreting cells. However, we observe that the presence and amount of MT used during immunization have no effect on the frequency of usage, polarization and in vivo expansion of cells carrying the studied rearrangements. Rather, the strong Th1-promoting effect of adjuvant is possibly due to recruitment toward Th1 of a wider spectrum of TCR repertoires. Therefore, instead of having a comprehensive effect on the entire repertoire, MT modulates the immune response by affecting a subset of antigen-specific T cells whose polarization can be adapted to the environment. This step establishes the final balance between Th1 and Th2 and may be essential for the enhancement or protection of disease.

Keywords: EAE, Mycobacterium tuberculosis, TCR, Th1/Th2 cells

Transmitting editor: S. Romagnani


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