CUTTING EDGE - CD40 LIGAND IS NOT ESSENTIAL FOR THE DEVELOPMENT OF CELL-MEDIATED-IMMUNITY AND RESISTANCE TO MYCOBACTERIUM-TUBERCULOSIS

It has been proposed that the induction of cellular immunity and resis tance to intracellular pathogens is dependent upon CD40 ligand (CD40L) , In the present study we show that this proposal is not ubiquitously supported, Mice genetically deficient in CD40L (CD40LKO) were resistan t to i.v. infection with Mycobacterium tuberculosis when assessed by s urvival and bacteriologic burden in the spleen, liver, and lungs, Infe cted CD40LKO mice developed granulomas that lacked epithelioid cells a nd were less numerous and markedly smaller than those observed in cont rol mice, Upon stimulation with purified protein derivative of M. tube rculosis, CD4(+) T cells from infected CD40LKO mice proliferated and p roduced high levels of IFN-gamma but not IL-4, Finally, spleen cells f rom CD40LKO mice stimulated with M. tuberculosis produced IL-12, TNF, and nitric oxide levels comparable to those produced by control cells, In contrast to original proposals, these data clearly show that prote ctive Th1 immunity can be achieved against intracellular pathogens (e. g., Mycobacterium) independently of CD40L.