In situlocalization of T lymphocyte subsets in human paracoccidioidomycosis

Abstract

lmmunohistochemical techniques using monoclonal antibodies to T lymphocyte subsets were used to characterize granulomas caused by Paracoccidioides brasiliensis. Punch biopsies of skin or mucosa from eight patients and of lymph nodes from two patients with disseminated paracoccidioidomycosis were studied. The T lymphocytes were distributed either in a localized pattern related to epithelioid granulomas or in a diffuse arrangement, predominantly around the vessels. In the granulomas, T cells formed a peripheral mantle surrounding central aggregates of macrophages. The majority of lymphocytes were T-helper cells with few suppressor cells. In contrast, patients presented with a decreased number of peripheral Thelper lymphocytes and a corresponding decrease in helper-suppressor cell ratios. There was no clear-cut relationship between tissue helper-suppressor cell ratios and the level of cellular immunodepression of the patients. The lowest P. brasiliensis antibody titers were detected in patients with the highest tissue helper-suppressor cell ratios. The distribution pattern of T lymphocytes in P. brasiliensis granulomas, with a predominance of helper phenotype, suggests that these cells are actively involved in the disease process.Paracoccidioidomycosis is a systemic disease caused by Paracoccidioides brasiliensis and is characterized mainly by involvement of the skin, mucosa, lungs, lymph nodes and adrenal glands. The histopathologic findings consist of epithelioid granulomatous inflammation with variable numbers of lymphomononuclear and polymorphonuclear cells.It has previously been shown that T lymphocytes from patients with paracoccidioidomycosis have a decreased reactivity to P. brasiliensis antigens, unrelated common antigens and mitogens, by several tests in vivo and in vitro [13]. The cell-mediated immunosuppression has been explained by a variety of potential mechanisms including host-produced serum-factors, immune complexes and suppressor cell populations [1,12,13].

Depletion of CD8+T Cells In Vivo Impairs Host Defense of Mice Resistant and Susceptible to Pulmonary Paracoccidioidomycosis

“…Some authors observed decreased numbers of CD4 ϩ and CD8 ϩ T cells (30), whereas others reported a decrease only in the CD4 ϩ subset (2). The mucous and skin granulomatous lesions of PCM patients presented an elevated CD4/CD8 T-cell ratio due to high numbers of infiltrating CD4 ϩ T cells; this ratio in the blood, however, was very low (29). These findings showed that the phenotype of cells found in the blood does not reflect the subsets infiltrating the lesions.…”

Paracoccidioidomycosis: an update

“…Immunohistochemical staining techniques using monoclonal antibodies specific for CD4 and CD8 T cells revealed a predominance of CD4 T cells in granulomas from patients with the acute and chronic forms of the disease (200). CD4/CD8 ratios in granulomas were higher in biopsy samples from lymph nodes (3.8 to 4.0) and skin (1.27 to 4.27) than in those from mucosa (1.01 to 2.76).…”

“…A strong argument in support of this hypothesis is that impairment of cell-mediated responses is reversible by successful therapy (197,264). The search for a factor(s) responsible for negative immunoregulation of cellular immunity during paracoccidioidomycosis has ranged from unidentified inhibitory factors in patient plasma (208,264) and immune complexes (9,68,69,304) to an imbalance in T-cell subsets (200,204).…”

Differential gene expression analysis of Paracoccidioides brasiliensis during keratinocyte infection

“…Oral mucosal lesions are commonly multiple, with a granular, mulberry-like surface and microulcerations, and microscopically are observed as a granulomatous inflammatory reaction and pseudoepitheliomatous hyperplasia that can be mistaken as neoplastic (Kaminagakura et al, 2006;Moscardi-Bacchi et al, 1989;Scully & de Almeida, 1992), which can be a problem clinically as the oral lesions of PCM closely resemble carcinoma (Kaminagakura et al, 2006). The fungus may use a sequence of different mechanisms to become established in the host, from the first contact with host cells until the later stages of the disease.…”