T lymphocyte and monocyte interaction by CD40/CD40 ligand facilitates a lymphoproliferative response and killing of Cryptococcus neoformans in vitro.
This study explored the role of CD40 / CD40 ligand (CD40L) in the induction of a lymphoproliferative response and killing of Cryptococcus neoformans in vitro. In our experimental system, monocytes exposed to C. neoformans were used as antigen-presenting cells (APC) and co-cultured with autologous T cells. The results showed that CD40 / CD40L strongly regulated the blastogenic response of T cells to C. neoformans. The fungus up-regulated CD40 expression on APC. An acapsular strain appeared to be a better inducer than an encapsulated strain. Time course experiments showed optimal regulation of CD40 expression at 48 h of incubation. Blocking the interaction of CD40 on APC with CD40L on T cells using mAb to CD40L resulted in a significant inhibition of IFN-gamma production. The anti-cryptococcal activity of monocytes was greatly influenced by the CD40 / CD40L interaction, and a positive correlation was found between nitric oxide secretion and enhanced killing of C. neoformans. Finally, the CD40 / CD40L interaction was critical for induction of optimal secretion of pro-inflammatory cytokines such as TNF-alpha and IL-1beta. These results indicate an important role for CD40 / CD40L interaction in inducing activation of T cells. Such cell-to-cell contact promotes anti-cryptococcal activity as well as secretion of pro-inflammatory cytokines by monocytes.
Vecchiarelli
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A
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy. vecchiar@unipg.it
Retini
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C
Pietrella
D
D
Monari
C
C
Kozel
T R
TR
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand