T-cell dysfunction and hyperimmunoglobulinemia E in paracoccidioidomycosis

Abstract

Various aspects of T and B cell mediated immunity were investigated in 20 well documented cases of active (10) or inactive (10) paracoccidioidomycosis (Pcm), as well as in 8 healthy individuals living in the endemic area of the disease. The results confirm previous reports that active Pcm produces diverse grades of depression of T cell mediated immunity. Such T cell dysfunction is not associated with a reduction in the number of peripheral E rosette-forming cells, and the immunodepression is reversed by chemotherapy. Sera from Pcm (active or inactive) patients have significantly increased levels of total IgE, but the actual proportion of IgE antibodies against P. brasiliensis was very low (0.4-0.6%). The highest levels of total IgE were found in active patients with disease-related immune depression, suggesting that T cell dysfunction might contribute to the excessive IgE production.

An overview of the immunopathology of human paracoccidioidomycosis

“…Immunological description: the lymphoproliferative response, the cytokine balance and the monocytes Studies published mainly in the 1970s and 1980s have shown depressed cellular immune responses of PCM patients, usually employing the lymphocyte proliferation and/or leukocyte migration inhibition tests [9][10][11][12][13][14][15][16]. They have shown that the cellular arm of the immune responses is affected both in a specific (elicited by P. brasiliensis components) and a nonspecific fashion (elicited by microbial antigens other than Pb or mitogens).…”

“…In disagreement with some studies, but in agreement with others, we observed that the majority of the patients with PCM presented overall adequate T cell responses to mitogens (and to a Pb-unrelated fungal antigen). These studies are summarized in Table 1 [9][10][11][12][13][14][15][16][21][22][23][24][25][26].…”

Vaccination with Heat Shock Protein 60 Induces a Protective Immune Response against ExperimentalParacoccidioides brasiliensisPulmonary Infection

“…Specific T-cell-mediated immune responses play a fundamental role in the resistance to P. brasiliensis. Compared to individuals with localized disease, patients with systemic PCM display several defects in cellular immunity characterized by impaired in vivo delayed type hypersensitivity reactivity, alterations in the ratio of CD4 ϩ /CD8 ϩ cells, an imbalance in cytokine levels, and a depressed in vitro T-cell proliferation to fungal antigens (2,5,6,7,11,37,38).…”

Capture enzyme-linked immunosorbent assay to detect specific immunoglobulin E in sera of patients with paracoccidioidomycosis.

“…1,3 Elevated serum IgE has also been found in patients with fungal infection such as blastomycosis, coccidioidomycosis, and paracoccidioidomycosis (PCM). [4][5][6] Experimental evidence strongly suggests that in humans, PCM resistance and susceptibility may be associated with a Th1 and Th2 pattern of cytokines, respectively. 7,8 Considering that the isotypes of the immunoglobulins are determined by the patterns of cytokines present in microenvironment where B cells are being activated, the detection of particular isotypes may be considered as indicators of the corresponding pattern of inductive cytokines.…”