Evidence For Early Aging in the Mucosal Immune System

Abstract

Despite recent advances in the cellular and molecular analysis of induction and regulation of mucosal immune responses, little is yet known about differences which occur in aging. To address this important issue, we have compared the mucosal and systemic immune responses of aged (12- to 14-mo- or 2-year-old) and young adult (6- to 8-wk-old) C57BL/6 mice. Both aged and young mice were immunized weekly with three oral doses of 1 mg of OVA and 10 μg of cholera toxin (CT) as mucosal adjuvant. Both groups of mice over 1 or 2 years of age showed reduced levels of Ag-specific mucosal or systemic immune responses at day 21. An Ag-specific B cell enzyme-linked immunospot assay confirmed these results at the cellular level. When the Ag-induced cytokine responses were examined at both protein and mRNA levels, CD4+ T cells from spleen and Peyer’s patches of young adult mice revealed elevated levels of IL-4 production; however, these cytokine responses were significantly diminished in aged mice. In contrast to mucosal immunization, mice s.c. immunized with OVA plus CT resulted in impaired OVA-specific but intact CT B subunit-specific immune responses in 12- to 14-mo-old mice although the responses to both Ags were depressed in 2-year-old mice. These results provide the first evidence that the development of age-associated alterations possibly occurs earlier in the mucosal immune system than in the systemic immune compartment.

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

“…In mice, some reports suggest that, with ageing, the levels of total and specific serum IgG and IgM increase (Koga et al, 2000), while other authors found a reduction in specific IgG and IgM in aged animals (Faria et al, 1998). Speziali et al (2009), have recently shown that basal levels of total serum immunoglobulins, IgG and IgA were increased while antigen-specific immunoglobulins, IgG and IgA were reduced in aged mice compared to young ones.…”

“…Speziali et al (2009), have recently shown that basal levels of total serum immunoglobulins, IgG and IgA were increased while antigen-specific immunoglobulins, IgG and IgA were reduced in aged mice compared to young ones. This divergence between total and specific levels of Immunoglobulins, IgG and IgA may reflect the biased repertoire of B cells in aged mice (Koga et al, 2000) and their inability to mount specific immune responses to new antigens. Moreover it has been shown that ageing is followed by an increased production of auto-antibodies in parallel with a diminished production of antibodies against foreign antigens (Weksler and Szabo, 2000).…”

Production of vaccines and vaccine components in corn

“…Co-administration of adjuvants can increase immunogenicity of mucosally administered antigens (Fujihashi et al, 2000, Kanellos et al, 2000, Choi et al, 2002. Two such mucosal adjuvants, heat labile enterotoxin (LT) from enterotoxinogenic strains of Escherchia coli and its homologue cholera toxin (CT) from…”

“…Besides potential use as mucosal adjuvants, the two B-subunits can also serve as vaccines against diarrhea caused by LT and CT as the B-subunit induces high levels of anti-LT-B and anti-CT-B secretory IgA that provide protection against subsequent toxin challenge (Haan et al, 1996, Verweij et al, 1998, Guidry et al, 1997. In addition, our previous studies indicate that oral administration of LT-B corn can induce significant concentrations of anti-LT-B IgG in serum (Fujihashi et al, 2000). For example, vaccines against influenza and tuberculosis are less efficient in aged individuals when compared to young adults (Mayer, 2000.…”

“…For example, vaccines against influenza and tuberculosis are less efficient in aged individuals when compared to young adults (Mayer, 2000. Aged mice that were given CT and CT-B as an adjuvant for the co-administered antigen ovalbumin demonstrate a diminished capacity to produce antigen specific antibodies mucosally (IgA) and systemically (IgG) when compared to young mice (Fujihashi et al, 2000, Nagler-Anderson et al, 1986). …”