CTLA-4 blockade enhances the immune response induced by mycobacterial infection but does not lead to increased protection

The murine immune response to a pulmonary mycobacterial infection is slow t o develop, allowing bacterial numbers to increase in the lung for several w eeks after infection. We sought to enhance the protective immune response i nduced during Mycobacterium bovis BCG infection by administering an antibod y that blacks the interaction of CTLA-4 with its ligands, CD80 and CD86. We found that injection of anti-CTLA-4 monoclonal antibody (MAb) greatly enha nced and accelerated the immune response, as measured by increased cellular ity of the draining mediastinal lymph nodes, and enhanced antigen-inducible proliferation and gamma interferon production by mediastinal lymphocytes i n vitro. However, despite the apparently enhanced immune response in the me diastinal lymph node following treatment with anti-CTLA-4 MAb, there was no improvement in clearance of mycobacteria in the lungs, liver, or spleen. E xamination of the primary site of infection, the lung, revealed that CTLA-4 blockade had no effect on the number or function of lymphocytes infiltrati ng the infected lung tissue. Taken together, these data suggest that in viv o CTLA-4 blockade enhances mycobacterial-infection-induced lymphocyte expan sion and effector cell cytokine production in the draining lymph node but d oes not alter the number or function of lymphocytes at the primary site of infection and therefore does not lead to enhanced clearance of the infectio n.