RESUMO
Paracoccidioidomycosis patients show hyperactive humoral immune responses. Consequently, we investigated whether cytokines in supernatants from Paracoccidioides brasiliensis-stimulated gamma/delta T cells support B-cell activation. We detected proliferation of B cells and increased immunoglobulin M (IgM) and IgG production. Thus, gamma/delta T cells may participate in polyclonal B-cell activation during paracoccidioidomycosis.
Assuntos
Linfócitos B/imunologia , Paracoccidioides/imunologia , Subpopulações de Linfócitos T/imunologia , Anticorpos Antifúngicos/biossíntese , Formação de Anticorpos , Antígenos de Fungos/imunologia , Humanos , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T gama-delta/imunologiaRESUMO
Paracoccidioides brasiliensis causes a chronic granulomatous mycosis, prevalent in South America, and cell-mediated immunity represents the principal mode of protection against this fungal infection. We investigated the response of naive cord blood T cells to P. brasiliensis lysates. Our results show: (1) P. brasiliensis stimulates T-cell expansion, interleukin-2 (IL-2) production and differentiation into cytotoxic T cells; (2) T-cell stimulation depends on P. brasiliensis processing and major histocompatibility complex (MHC) class II expression; (3) the responsive T-cell population expresses alpha beta T-cell receptors (TCR) with different V beta gene products, CD4 and CD45RO; (4) the P. brasiliensis components involved in T-cell expansion primarily reside in a high molecular weight (100,000 MW) and a low molecular weight (< 1000 MW) protein fraction. These results indicate that protein antigens of P. brasiliensis stimulate cord blood CD4 alpha beta T cells, independent from in vivo presensitization, and thus question direct correlation of positive in vitro responses with protective immunity in vivo.
Assuntos
Antígenos de Fungos/imunologia , Linfócitos T CD4-Positivos/imunologia , Sangue Fetal/imunologia , Paracoccidioides/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Células Cultivadas , Antígenos HLA-DR/imunologia , Humanos , Interleucina-2/biossíntese , Ativação Linfocitária , Fenótipo , Linfócitos T Citotóxicos/imunologiaRESUMO
Paracoccidioides brasiliensis, a dimorphic fungus, causes chronic granulomatous mycosis in susceptible individuals. Different reports have shown that cell-mediated immunity is essential for protection against systemic mycosis, including paracoccidioidomycosis. We analyzed the reactivity of alpha beta and gamma delta T cells from unexposed Caucasian donors to P. brasiliensis yeast form components. Our results indicate: (i) alpha beta and gamma delta T cells proliferate after in vitro stimulation with lysates of P. brasiliensis; (ii) similar numbers of alpha beta T cells (f = 1/21,000) and of gamma delta T cells (f = 1/8000) respond to P. brasiliensis; (iii) P. brasiliensis-reactive gamma delta T cells express the V gamma 9V delta 2 TCR; (iv) the stimulatory activity of P. brasiliensis for both alpha beta and gamma delta T cells primarily resides in a high molecular weight (100 kDa) and in a low molecular weight (< 1 kDa) fraction; (v) the ligands responsible for stimulation of both alpha beta and gamma delta T cells are sensitive to proteinase treatment. We conclude that both alpha beta and gamma delta T cells from healthy individuals respond to ubiquitous protein antigens of P. brasiliensis.
Assuntos
Antígenos de Fungos/imunologia , Paracoccidioides/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Subpopulações de Linfócitos T/imunologia , Apresentação de Antígeno/imunologia , Endopeptidase K , Citometria de Fluxo , Humanos , Interleucina-2/biossíntese , Ativação Linfocitária , Serina EndopeptidasesRESUMO
Immunity to intracellular bacteria including Mycobacterium tuberculosis, Mycobacterium leprae, and Listeria monocytogenes depends on specific T cells. Evidence to be described suggests that CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells which interact with each other and with macrophages contribute to acquired resistance against as well as pathogenesis of intracellular bacterial infections.