The role of activated TCD8+ cells in the experimental infection with Paracoccidioides brasiliensis and Paracoccidioides lutzii.

Abstract

The thermo-dimorphic fungus Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), systemic mycosis endemic in several countries in Latin America, in Brazil occurs in almost all regions, with higher prevalence in South, Southeast, Midwest and North. The primary site of infection is the lung which may spread to other organs and tissues. Secondary lesions may be found in the mucous membranes, skin, lymph nodes, liver, spleen and adrenal gland often leading to permanent sequelae. The immunodominant antigen of P. brasiliensis is a glycoprotein known as gp43. The gp43 has epitopes for T and B cells that determine the progress of the infection. Several authors have demonstrated the crucial role of CD4 + T cells in resistance to PCM, however little is known about the role of CD8 + T cells in infection. Previous work showed that depletion of CD8 + T cells induces a greater spread and severity of PCM in susceptible and resistant mice. Most of the isolates belong to three phylogenetic groups: S1, PS2 and PS3. A new group (Pb01-like) was recently identified and named Paracoccidioides lutzii and studies in our laboratory showed that the major antigen gp43 is not isolated but a molecule of approximately 66 kDa. The phylogenetic differences among isolates Pb01 and Pb18 may reflect differences in disease development and response to antifungal treatments. Therefore this project aims to identify the epitopes for CD8 + T cells present in the gp43 of P. brasiliensis antigen and also in the majority of P.lutzii. In a second stage, will be evaluated "in vivo" and "in vitro" activity of CD8 + T cells in infection in the absence or presence of CD4 + T cells, induction of memory cells and the potential vaccine peptides capable of stimulating CD8 + T cells with or not the activation of CD4 + T cells.