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International Immunology, Vol. 11, No. 6, 899-906, June 1999
© 1999 Japanese Society for Immunology

Expansion of neonatal tolerance to self in adult life: I. The role of a bacterial adjuvant in tolerance spread

Nir Grabie1, Ishay Wohl1, Sawsan Youssef1, Gizi Wildbaum1 and Nathan Karin1,2

1 Department of Immunology, Bruce Rappaport Faculty of Medicine and
2 Rappaport Family Institute for Research in the Medical Sciences, Technion, POB 9697, Haifa 31096, Israel

Correspondence to: N. Karin

T cell neonatal tolerance to self evolves perturbation of the Th1/Th2 balance towards Th2-type self-specific T cells. In the current study we have demonstrated that a tolerant state could be extended to another encephalitogenic determinant only if the neonatally tolerizing determinant was co-administered in adult life with an emulsion of Mycobacterium tuberculosis (i.e. complete Freund's adjuvant). The mechanisms underlying tolerance elicitation and expansion were then explored by an in vitro system in which indirect suppression could be measured. Addition of a tolerizing epitope to splenic T cells from neonatally tolerized animals induced a marked suppression of the anti-MT response. This response could be restored by neutralizing antibodies to IL-4. In contrast, the neutralizing antibodies to IL-4 had no affect on the response of these cells to the tolerizing determinant. These findings are highly significant not only because they explore the important role of microbial antigens in neonatal tolerance, but also because they distinguish, for the first time, between tolerizing and tolerized T cells.

Keywords: complete Freund's adjuvant, determinant spreading, experimental autoimmune encephalomyelitis, Mycobacterium tuberculosis, myelin basic protein, neonatal tolerance

Transmitting editor: L. Steinman


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