Cellular basis of differential responsiveness of lymph nodes and spleen to 23-valent Pnu-Imune vaccine

Subcutaneous administration with 23-valent pneumococcal polysaccharide vaccine (Pnu-Imune) elicited a good antipneumococcal capsular polysaccharide response from the spleen but not from peripheral lymph nodes (LN) (cervical, brachial, axillary, popliteal, inguinal) of BALB/c mice. To evaluate the cellular basis of the unresponsiveness of LN to this vaccine and to identify the cell types in spleen that are necessary for induction of polysaccharide Ab responses, a reliable in vitro culture system was developed to obtain plaque-forming cell responses to the Pnu-Imune vaccine. The in vitro antipneumococcal polysaccharide response of mouse spleen cells was found to be relatively T cell independent. Unlike spleen cells, LN cells did not respond to the Pnu-Imune vaccine in vitro. However, LN cells responded to Pnu-Imune vaccine when co-cultured with irradiated spleen cells or splenic dendritic cells but not with accessory cell-depleted spleen cells. LN cells were found to contain the necessary accessory cells that can support the polysaccharide response but in reduced numbers. The LN response to the vaccine was also reconstituted by IL-1 or Th2-associated cytokine IL-5. In contrast, IFN-gamma, a Th1 cell-derived lymphokine was able to suppress the in vitro splenic response to the vaccine suggesting that differential activation of Th1 and Th2 types of Th cells might be one mechanism by which T cells regulate Ab responses to pneumococcal polysaccharides.