Cellular basis of decreased immune responses to pneumococcal vaccines in aged mice.

Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152: 1589-1596, 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studies showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell deficiency. Irradiated spleen cells from young mice enabled the old mouse spleen cells to respond to the vaccine. Interestingly, irradiated spleen cells from old mice also restored the vaccine responsiveness in old mice but were required in greater numbers than the young mouse spleen cells to induce similar levels of response. The accessory cell was an adherent cell that could be removed by passage through Sephadex G-10 and thus may be a macrophage. Accessory function could also be provided by the cytokine interleukin-1 (IL-1), IL-4, or IL-5 but not IL-2 or IL-6. Thus, one reason for the deficient immune response to pneumococcal vaccine in aged mice is a quantitative defect in adherent accessory cells.