Contagious bovine pleuropneumonia (CBPP), due to MmmSC, is still an important disease in Africa where the only realistic prophylaxis is vaccination. This study was implemented to acquire the immunological basis to develop new vaccines against CBPP. Zebus were experimentally infected and classified according to the clinical form of CBPR: acute, chronic or resistant. Blood cells were regularly taken and phenotyped by flow cytometry. MmmSC-specific responsiveness was then studied by in vitro assays and responding cells characterised by flow cytometry. The kinetics revealed a blood T-cell response in resistant animals and a dominant B-cell response in clinically-ill zebus. However, all zebus were characterised by an in vitro MmmSC-specific response mainly based on CD4 T-cells with IFNy released. These results suggested that susceptibility to CBPP is associated in vivo with an impair immune response possibly due to a down regulation by B or accessory cells. In contrast, resistance appeared to be linked with the development of an efficient CD4 T-cells response secreting IFNy.