Human alveolar macrophages induce functional inactivation in antigen-specific CD4 T cells.
BACKGROUND
Alveolar macrophages (AMCs) are the most abundant phagocytic cells in the lung, but they present antigen poorly to T cells.


OBJECTIVE
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.
Blumenthal
R L
RL
Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Calif 94305-5208, USA.
Campbell
D E
DE
Hwang
P
P
DeKruyff
R H
RH
Frankel
L R
LR
Umetsu
D T
DT
D000069594:Abatacept; D000917:Antibody Formation / Q000276:immunology; D017951:Antigen Presentation / Q000502:physiology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D000939:Epitopes / Q000502:physiology; D006801:Humans; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000502:physiology*; D011014:Pneumonia / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000939:Epitopes; D018796:Immunoconjugates; D000069594:Abatacept