Effect of Adjuvants on Response to Pneumococcal Polysaccharide Injected Intraperitoneally Platelet-Derived Immunoregulatory Activity

摘要

A platelet-derived factor was described which reserves both antigen specific and nonspecific (Con A induced) suppression of antibody production in mice. The factor was indentified as a granule derived platelet factor 4 (PF4). Immunoregulatory activity of PF4 was found to be dependent on the presence of a proteolytic enzyme during its release form platelets. Both mouse and human PF4 from platelet released and from serum are absorbed by a T cell subset from mouse lymph node and spleen, but not from thymus, with surface characteristics of suppressor T cells. Con A induced splenic suppressor cells adhere to dishes coated with PF4. However, PF4 or platelet released do not reverse Con A induces suppression in vitro. In view of the known tendency of PF4 to adhere to heparan sulfate in the blood vessel wall, it is suggested that PF4 changes distribution of suppressor cells in vivo, thereby interfering with their activity. Various adjuvants were examined for their ability to affect the serum antibody response to pneumoccal polysaccharides (pps) types 3 and 14. Detoxified endotoxin, lectins and lymphokine mixtures all enhance the response to pps when injected 2-4 days after pps. Coupling of MTP to pps renders it more immunogenic, as does emulsifying pps with Nor-MDP in squalene arlacel. IgD injected together with pps 14, or 1 week before, enhances both primary and secondary responses, particularly to subimmunogenic doses.