Control of latent Mycobacterium tuberculosis infection is dependent on CD8T cells

It is estimated that one-third of the world's population is infected with M ycobacterium tuberculosis, but that only 10% of infected people break down with the disease. In the remaining 90% the infection remains clinically lat ent. In the present study, the immune mechanisms controlling the latent pha se of tuberculosis infection were evaluated in a mouse model of latency and reactivation. Mice aerosol-infected with M. tuberculosis were treated with anti mycobacterial drugs resulting in very low, stable bacterial numbers ( <500 CFU in the spleen and lung) for 10-12 weeks followed by reactivation o f the disease with increasing bacterial numbers. During latency, pathologic al changes in the lung had almost completely resolved and lymphocyte number and turnover were at the pre-infection level. The CD4 subset was highly ac tive during the acute phase of infection and could be detected by intracell ular staining for IFN-<gamma> as well as after antigen-specific stimulation with mycobacterial antigens. The CD8 subset was not involved in the acute stage of infection, but this subset was active and produced IFN-gamma durin g the latent phase of infection. In vivo depletion of T cell subsets suppor ted these findings with a 6-7-fold increase in bacterial numbers in the lun g following anti-CD4 treatment during the acute phase, while anti-CD8 treat ment did not have an effect. The opposite was found during the latent phase where anti-CD8 treatment as well as anti-IFN-gamma treatment both resulted in a 10-fold increase in bacterial numbers in the lung, while anti-CD4 tre atment induced only a modest change.