Infant CD4⁺ T-cell responses to bacterial infections or vaccines have been extensively studied, whereas studies on CD8⁺ T-cell responses focused mainly on viral and intracellular parasite infections. Here we investigated CD8⁺ T-cell responses upon Bordetella pertussis infection in infants, children, and adults and pertussis vaccination in infants. Filamentous hemagglutinin-specific IFN-γ secretion by circulating lymphocytes was blocked by anti-MHC-I or -MHC-II antibodies, suggesting that CD4⁺ and CD8⁺ T lymphocytes are involved in IFN-γ production. Flow cytometry analyses confirmed that both cell types synthesized antigen-specific IFN-γ, although CD4⁺ lymphocytes were the major source of this cytokine. IFN-γ synthesis by CD8⁺ cells was CD4⁺ T cell dependent, as evidenced by selective depletion experiments. Furthermore, IFN-γ synthesis by CD4⁺ cells was sometimes inhibited by CD8⁺ lymphocytes, suggesting the presence of CD8⁺ regulatory T cells. The role of this dual IFN-γ secretion by CD4⁺ and CD8⁺ T lymphocytes in pertussis remains to be investigated.