CELL-MEDIATED CORRELATES OF PROTECTIVE IMMUNITY IN Q FEVER: LYMPHOCYTE TRANSFORMATION AND CYTOKINE RELEASE BY SPLEEN CELLS FROM MICE IMMUNIZED WITH PHASE I OR PHASE II COXIELLA BURNETII WHOLE-CELL VACCINES

Abstract

Protective immunity against Coxiella burnetii, the causative agent of Q fever, depends primarily on cell-mediated immunity. Mice immunized with inactivated whole-cell vaccines (WCV) made from naturally occurring virulent phase I form of the organism were protected from lethal infection with 1000- fold lower vaccine doses than mice immunized with WCV made from the egg-passaged avirulent phase II form. To test the hypothesis of cytokine production correlation with protection from challenge, cytokines were measured. Spleen cell culture taken from mice immunized with various doses of WCV-Phase I (WCV-I) or WCV-Phase II (WCV-II) and stimulated with C. burnetii antigen in vitro was measured. The concentrations of interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor-a (TNF-a) and gamma interferon (IFN-y) were determined by ELISA from cell culture supernatants. For all four cytokines, spleen cell cytokine production was greater for mice immunized with WCV-I. Spleen cell supernatants from mice immunized with 100 Ag of WCV-I contained 2.1-, 5.2- and 5.3- fold greater concentrations of IFN-y, IL-6 and TNF-a, respectively, than spleen cell supernatants from mice immunized with 100 Ag of WCV-II. Supernatant production of these three cytokines from spleens of normal unimmunized mice ranged between 5 to 10 times lower than those from mice immunized with WCV-I. There was little difference in IL-2 production between mice immunized with 100 Ag WCV-I or WCV-II, but spleen cell supernatants from mice immunized with lower doses of WCV-I contained 2.2- to 3.1-fold greater concentrations of IL-2 than spleen cell supernatants from mice immunized with comparable low doses of WCV-II. These results are consistent with the hypothesis that the protective immunity induced by WCV-I may be correlated with greater cytokine production by immune T cells.