Development of specific and cross-reactive lymphocyte proliferative responses during chronic immunizing infections...

The development of antigen-responsive lymphocytes was followed in mice immunized with the Gilliam, Karp, or Kato strains of Rickettsia tsutsugamushi by utilizing an in vitro lymphocyte proliferation assay. Subcutaneous immunization with viable rickettsiae of all three strains resulted in the appearance of lymphocytes in the spleen responding to irradiated tissue culture-grown rickettsiae used as stimulating antigens. Although all animals demonstrated antigen-induced proliferation elicited by homologous antigen by 14 days after immunization, the time of peak responsiveness varied, depending on the strain of rickettsiae used for immunization. In all cases, peak proliferative responses occurred at a time after immunization that was after the previously reported time after immunization at which resistance to rechallenge was observed. Reactivity to heterologous strains of R tsutsugamushi developed roughly in parallel with homologous reactivity in Karp- and Gilliam-immunized mice, with a marked degree of heterologous reactivity evident. Kato-immunized mice demonstrated greater reactivity to heterologous antigens early in the development of antigen reactivity and demonstrated a somewhat greater degree of cross-reactivity, relative to homologous responses, than the other groups. It was found that nylon wool-nonadherent immune cells, if cultured with antigen and adherent cells obtained from normal spleens or peritoneal exudates, responded in culture. The thymus-derived lymphocyte nature of the responding cell was further suggested when treatment of immune spleen cells with anti-Thy 1.2 serum and complement eliminated antigen response.