Details

Autor(en) / Beteiligte

• Campanelli, Ana P
• Martins, Gislâine A
• Souto, Janeusa T
• Pereira, Marcelo S. F
• Livonesi, Márcia C
• Martinez, Roberto
• Silva, João S

Titel

Fas-Fas Ligand (CD95-CD95L) and Cytotoxic T Lymphocyte Antigen-4 Engagement Mediate T Cell Unresponsiveness in Patients with Paracoccidioidomycosis

Ist Teil von

• The Journal of infectious diseases, 2003-05, Vol.187 (9), p.1496-1505

Ort / Verlag

Chicago, IL: The University of Chicago Press

Erscheinungsjahr

2003

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• The mechanism that leads to the remarkable T cell unresponsiveness to antigens in paracoccidioidomycosis is unknown. We investigated the involvement of cytokines, of Fas-Fas ligand (Fas-FasL)-induced apoptosis, and of cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement, in the mediation of this phenomenon. T cell unresponsiveness was not associated with imbalanced cytokine production or with absence of CD28 expression. Only patient T cells expressed higher levels of CTLA-4, Annexin V+, and FasL. The addition of anti-FasL decreased the levels of apoptosis, suggesting an activation-induced cell death triggered through the Fas-FasL pathway. Blockage of CTLA-4 and FasL resulted in increased production of interferon-γ. Moreover, concomitant inhibition of FasL and of CTLA-4, but not of transforming growth factor-β, resulted in significant T cell proliferation in patients, in response to phytohemagglutinin. Together, these data show that apoptosis mediated by Fas-FasL and engagement of CTLA-4 are involved in modulation of the immune response in patients infected with Paracoccidioides brasiliensis