Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides small colony (MmmSC), is one of the most important bacterial epizootic in Africa. In order to better understand the basis of protective immunity and immunopathologic reactions associated with CBPP we have studied MmmSC-induced T-cell responses in draining lymph nodes of infected animals. Upon in vitro stimulation with inactivated MmmSC, two distinct populations of memory CD4 were activated as shown by up regulation of CD25: i)CD4+ central memory T (Tcm) cells characterized by high CD62L expression and proliferation, and no IFN-[gamma] production; ii)CD4+ effector memory T (Tem) cells characterized by low CD62L expression and proliferation, and IFN-[gamma] production. MmmSC-induced CD4+ T(cm) cells were observed only in animals controlling the disease (chronic CBPP) while CD4+T(em) cells were also present in animals that succumbed (acute CBPP). Interestingly, live MmmSC completely prevented the growth of CD4+T(cm) cells but not their activation nor that of CD4+T(em) cells. This immuno-inhibitory effect of MmmSC was not due to cytotoxicity as shown by IP and AnnexinV staining of CD4+ T-cells. The relevance of these findings for the development of better vaccines against CBPP is discussed.