Protective immunity to Bordetella pertussis requires both B cells and CD4(+) T cells for key functions other than specific antibody production

To investigate the fundamental nature of protective immunity to Bordetella pertussis, we studied intranasal immunization of adult mice with formalin-f ixed B. pertussis (FFBP), followed by aerosol B. pertussis challenge. Mice given two doses of FFBP intranasally completely cleared a subsequent pertus sis aerosol challenge from tracheae and lungs (defined as protection), but there was no correlation between levels of specific antibody and clearance of bacteria. Further, transfer of immune serum before aerosol challenge had minimal effects on bacterial burdens. However, pertussis-specific T cells producing interferon gamma but not interleukin 4 or interleukin 10 were det ected in draining lymph nodes of FFBP-immunized mice. Significantly, repeat ed immunization of B cell knockout (BKO) mice resulted in partial protectio n, and complete protect ion was reconstituted by transfer of pertussis-immu ne B cells; reconstituted BKO mice had little ii any detectable antipertuss is antibodies. Immunization of mice lacking all T cells or lacking CD4(+) T cells did trot lead to protection; in contrast, CD8(-) mice were protected . Mice depleted of CD4(+) T cells after immunization but before aerosol cha llenge, which thus had normal amounts of specific antibodies, were not opti mally protected. Taken together, these data indicate that protective immuni ty to pertussis is dependent on both CD4(+) T cells and B cells, and both c ell types provide significant functions other than specific antibody produc tion.