Abstract
Oral tolerance can be induced in some mouse strains by gavage or spontaneous ingestion of dietary antigens. In the present study, we determined the influence of aging and oral tolerance on the secretion of co-stimulatory molecules by dendritic cells (DC), and on the ability of DC to induce proliferation and cytokine secretion by naive T cells from BALB/c and OVA transgenic (DO11.10) mice. We observed that oral tolerance could be induced in BALB/c mice (N = 5 in each group) of all ages (8, 20, 40, 60, and 80 weeks old), although a decline in specific antibody levels was observed in the sera of both tolerized and immunized mice with advancing age (40 to 80 weeks old). DC obtained from young, adult and middle-aged (8, 20, and 40 weeks old) tolerized mice were less efficient (65, 17 and 20%, respectively) than DC from immunized mice (P < 0.05) in inducing antigen-specific proliferation of naive T cells from both BALB/c and DO11.10 young mice, or in stimulating IFN-g, IL-4 and IL-10 production. However, TGF-beta levels were significantly elevated in co-cultures carried out with DC from tolerant mice (P < 0.05). DC from both immunized and tolerized old and very old (60 and 80 weeks old) mice were equally ineffective in inducing T cell proliferation and cytokine production (P < 0.05). A marked reduction in CD86+ marker expression was observed in DC isolated from both old and tolerized mice (75 and 50%, respectively). The results indicate that the aging process does not interfere with the establishment of oral tolerance in BALB/c mice, but reduces DC functions, probably due to the decline of the expression of the CD86 surface marker.
Highlights
Dendritic cells (DC) are the main antigen-presenting cells involved in the initiation of the immune response against exogenous antigens by stimulating naive T cells [1], but they have been associated with the deletion or silencing of auto-reactive lymphocytes that leads to central and/or peripheral tolerance [2,3,4]
Influence of age on the humoral immune response of mice The humoral immune response of BALB/c mice (8, 20, 40, 60, and 80 weeks of age) was investigated as a function of oral treatment with OVA followed by an ip challenge or ip immunization, and the levels of specific serum antibodies were determined by enzyme-linked immunosorbent assay (ELISA)
Tcell enrichment The T cell populations were enriched from spleens of 8-week-old naive BALB/c or DO11.10 transgenic mice using the protocol of adhesion to nylon wool, as described previously [24]
Summary
Dendritic cells (DC) are the main antigen-presenting cells involved in the initiation of the immune response against exogenous antigens by stimulating naive T cells [1], but they have been associated with the deletion or silencing of auto-reactive lymphocytes that leads to central and/or peripheral tolerance [2,3,4]. In the context of tolerance, DC play an important role in the responses to exogenous antigens, mainly to dietary proteins, and in the inhibition of auto-reactive T cells that have escaped negative selection in the thymus [2,3]. It has been shown that DC generated from human peripheral blood can assume a tolerogenic function after treatment with IL-10, inhibiting allogenic mixed leukocyte reactions and the anti-CD3-induced response of primed and naive CD4+ T cells [6]. Other studies have shown that DC obtained from the gastrointestinal tract of mice do not present variations in the expression of the CD80 and CD86 molecules in oral tolerance or in priming with the antigen [8]
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