Depletion of CD8(+) T cells in vivo impairs host defense of mice resistantand susceptible to pulmonary paracoccidioidomycosis

Using a pulmonary model of infection, we demonstrated previously that A/Sn and B10.A mice are, respectively, resistant and susceptible to Paracoccidio ides brasiliensis infection. Employing the same experimental model, we exam ined herein the role of CD8(+) T cells in the course of paracoccidioidomyco sis. Treatment with anti-CDS monoclonal antibodies caused a selective deple tion of pulmonary and splenic CD8+ T cells in both mouse strains. The numbe r of pulmonary CD4(+) T cells and immunoglobulin-positive cells was indepen dent of the number of CD8(+) T cells. In susceptible mice, the loss of CD8( +) T cells by in vivo treatment with anti-CDS monoclonal antibodies impaire d the clearance of yeasts from the lungs and increased the fungal dissemina tion to the liver and spleen. The same treatment in resistant mice increase d fungal dissemination to extrapulmonary tissues but did not alter the pulm onary fungal load. Furthermore, CD8+ T-cell depletion did not modify delaye d-type hypersensitivity reactions of A/Sn mice but increased these reaction s in B10.A mice. The production of P. brasiliensis-specific antibodies by r esistant and susceptible mice depleted of CD8+ T cells was similar to that of mice given control antibody. Histopathologically, depletion of CD8(+) T cells did not disorganize the focal granulomatous lesions developed by both mouse strains. These results indicate that CD8(+) T cells are necessary fo r optimal clearance of the fungus from tissues of mice infected with P. bra siliensis and demonstrate more prominent protective activity by those cells in the immune responses mounted by susceptible animals.