Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules.
Alveolar macrophages, resident phagocytic cells in the lung that derive from peripheral blood monocytes, are paradoxically ineffective in presenting antigen to T cells. We found that antigen presentation by alveolar macrophages could be restored by the addition of anti-CD28 mAb to cultures of T cells and macrophages, indicating that costimulation by alveolar macrophages via the CD28 pathway was defective. In addition, we found that alveolar macrophages activated with IFN-gamma failed to express B7-1 or B7-2 antigens, which normally ligate CD28 on T cells and provide a costimulatory signal required for the activation of T cells. These observations are the first to demonstrate the inability of a "professional" antigen-presenting cell type to effectively express the costimulatory molecules B7-1 and B7-2. Inasmuch as immune reactions within the lung are inevitably associated with inflammatory injury to pulmonary tissue, these observations suggest that reduced expression of B7-1 and B7-2 by alveolar macrophages may be advantageous, as a critical mechanism involved in the induction of peripheral tolerance to the abundance of antigens to which mucosal tissues are continuously exposed.
Chelen
C J
CJ
Division of Allergy, Immunology, and Respiratory Medicine, Stanford University, Lucile Salter Packard Children's Hospital, California 94305-5119.
Fang
Y
Y
Freeman
G J
GJ
Secrist
H
H
Marshall
J D
JD
Hwang
P T
PT
Frankel
L R
LR
DeKruyff
R H
RH
Umetsu
D T
DT
D000328:Adult; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D018664:Interleukin-12