Modulation by cytokines of induction of oral tolerance to type II collagen

Objective, To determine whether the simultaneous administration of drugs an d/or cytokines such as transforming growth factor beta (TGF beta) can rende r oral tolerance to type II collagen (CII) more effective in causing resist ance to collagen-induced arthritis (CU) in mice, and to investigate whether oral tolerance can still be induced,when high levels of anti-CII are prese nt, Methods. Tolerance was induced by intragastric feeding of low-dose CIT to D BA/1 mice during a 2-week period, either before immunization with CII in Fr eund's complete adjuvant or after initiation of arthritis. Some mice were s imultaneously injected with TGF beta 1 or with the H-2 receptor agonist dim aprit, Results, Both TGF beta 1 and dimaprit increased the degree of oral toleranc e obtained. TGF beta 1 augmented the induction of immunoregulatory CD8 T ce lls, which transferred the resistance to CU induction to normal recipients. Feeding of CII for 2 weeks, starting after the onset of arthritis, still s ignificantly ameliorated the course of CU. Conclusion. Administration of TGF beta 1 or dimaprit, both of which are bel ieved to promote the development of immunoregulatory T cells, may reinforce induction of oral tolerance, even after the onset of arthritis.