BACKGROUND: Alveolar macrophages (AMCs) are the most abundant phagocytic cells in the lung, but they present antigen poorly to T cells. OBJECTIVES: The objectives of our studies were to more clearly define the mechanisms by which AMCs present antigen to T cells and to determine whether AMCs actively inhibit T-cell activation. METHODS: We studied purified human CD4 T cells and compared the capacity of allogeneic AMCs and peripheral blood monocytes to induce T-cell proliferation and cytokine production. RESULTS: We previously demonstrated that human AMCs fail to upregulate expression of B7-1 and B7-2 on stimulation with IFN-gamma. We now demonstrate that AMCs actively induce T-cell unresponsiveness (functional inactivation) in an antigen-specific manner and reduce the capacity of CD4 T cells to respond on secondary stimulation. The induction of unresponsiveness was reversed by the addition of CD28 costimulation or IL-2. However, interruption of Fas/Fas ligand interactions or of B7/CTLA-4 interactions did not prevent unresponsiveness, indicating that neither CTLA-4 triggering nor Fas-induced apoptosis was involved in the induction of T-cell unresponsiveness. CONCLUSIONS: These studies indicate that AMCs actively tolerize CD4 T cells in an antigen-specific fashion. We propose that AMCs mediate a form of immune privilege in the lungs that effectively limits immune responses in the pulmonary compartment but has little effect on systemic immunity.
BACKGROUND: Alveolar macrophages (AMCs) are the most abundant phagocytic cells in the lung, but they present antigen poorly to T cells. OBJECTIVES: The objectives of our studies were to more clearly define the mechanisms by which AMCs present antigen to T cells and to determine whether AMCs actively inhibit T-cell activation. METHODS: We studied purified human CD4 T cells and compared the capacity of allogeneic AMCs and peripheral blood monocytes to induce T-cell proliferation and cytokine production. RESULTS: We previously demonstrated that human AMCs fail to upregulate expression of B7-1 and B7-2 on stimulation with IFN-gamma. We now demonstrate that AMCs actively induce T-cell unresponsiveness (functional inactivation) in an antigen-specific manner and reduce the capacity of CD4 T cells to respond on secondary stimulation. The induction of unresponsiveness was reversed by the addition of CD28 costimulation or IL-2. However, interruption of Fas/Fas ligand interactions or of B7/CTLA-4 interactions did not prevent unresponsiveness, indicating that neither CTLA-4 triggering nor Fas-induced apoptosis was involved in the induction of T-cell unresponsiveness. CONCLUSIONS: These studies indicate that AMCs actively tolerize CD4 T cells in an antigen-specific fashion. We propose that AMCs mediate a form of immune privilege in the lungs that effectively limits immune responses in the pulmonary compartment but has little effect on systemic immunity.
Authors: Ivan K Chinn; John A Olson; Michael A Skinner; Elizabeth A McCarthy; Stephanie E Gupton; Dong-Feng Chen; Francisco A Bonilla; Robert L Roberts; Maria G Kanariou; Blythe H Devlin; M Louise Markert Journal: J Allergy Clin Immunol Date: 2010-09-15 Impact factor: 10.793
Authors: Daniel Silberman; Amanda Bucknum; Thomas Bartlett; Gabriella Composto; Megan Kozlowski; Amanda Walker; Amy Werda; Jackelyn Cua; Arlene H Sharpe; John E Somerville; James E Riggs Journal: Cell Mol Immunol Date: 2012-04-23 Impact factor: 11.530