Open AccessImportance of dose of type II collagen in suppression of collagen‐induced arthritis by nasal tolerance
Author(s) -
Derry Catherine J.,
Harper Nicola,
Davies D. Huw,
Murphy John J.,
Staines Norman A.
Publication year - 2001
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(200108)44:8<1917::aid-art330>3.0.co;2-w
Subject(s) - cytokine , arthritis , immune system , type ii collagen , immunology , t cell , medicine , interferon gamma , antibody , t lymphocyte , antigen , lymphocyte , endocrinology
Objective To determine the influence of the dose of collagen given nasally on the induction of specific mucosal tolerance in collagen‐induced arthritis. Methods The severity of clinical arthritis induced in DBA/1 mice was studied after the nasal administration (before disease induction) of 1 of 4 doses (across a 2‐log range) of bovine type II collagen (CII). Parameters of immunity included lymphocyte proliferation and cytokine production in vitro in response to antigen stimulation, and the production of anticollagen IgG antibody subclasses. Results The 3 highest doses (20, 80, and 320 μg) ameliorated disease severity, whereas the lowest dose (5 μg) aggravated disease. These findings correlated well with antigen‐specific T cell proliferation and cytokine and antibody production. T cell proliferation was suppressed by the higher doses of CII, whereas the low dose enhanced T cell proliferation, indicating it primed the T cells. Suppression of T cell proliferation could be overcome by the addition of exogenous interleukin‐2 (IL‐2) to these cultures. Decreased T cell proliferation was associated with suppression of both Th1 (interferon‐γ [IFNγ]) and Th2 (IL‐4) cytokines and all the subclasses of anticollagen IgG in mice receiving 20, 80, or 320 μg of collagen. Overall, the highest dose of collagen (320 μg) was less effective at suppressing the immune response and disease than the 20‐μg or 80‐μg doses. There was an increased production of antibodies of all IgG isotypes, and of the Th1‐associated cytokines IFNγ and IL‐2, in animals that had received the lowest dose of 5 μg collagen nasally. Conclusion Nasal administration of antigens is effective in inducing tolerance and reducing disease severity, but the effects are dose dependent. Low doses can prime the immune system and aggravate disease; high doses may not suppress disease. Suppression of the immune response, which correlates with suppression of disease, is not obviously associated with a type I to type II T cell switch, but rather with an overall suppression of both forms of T cell response, with a potential role for anergy of T cells in this process.