Impaired humoral immune responses to mycobacterial antigen in aged murine gut-associated lymphoid tissues

Senescence-related alterations of local gut mucosal immune responses to enteric mycobacterial antigen (Ag) were examined. Both aged (greater than 24 months old) and young adult (4-5 months old) BALB/c mice were enterically immunized with crude Mycobacterium paratuberculosis (M. paratbc) protoplasmic Ag, and in vitro Ag- and class-specific immunoglobulin (g) production by lymphocytes from gut-associated lymphoid tissues (GALT) (Peyer's patches, PP; mesenteric lymph nodes, MLN) and non-GALT (spleen, SPN) were determined against semipurified M. paratbc Ag. Ag-specific spontaneous immunoglobulin production by aged B cells from both GALT and non-GALT was enhanced only to a minor extent. Similarly, the functional activity of the Ag-specific T (Th) (CD3+, CD4+) cell in both GALT and non-GALT was not profoundly affected by senescence (qualitative preservation). However, that of the suppressor T (Ts) (CD3+, CD8+) cell was considerably diminished (qualtative defect). Thus, oral tolerance (systemic immunologic hyporesponsiveness) to M. paratbc Ag in aged mice is impaired. These age-related changes, manifested as hyperreactive humoral responses to the enteric microbial Ag, are due, at least in part, to hyporeactivity of the Ts cell, resulting in relative hyperfunction of the Ag-specific Th cell, despite the quantitative defect of the latter cell.