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. 1995 Mar;95(3):1415–1421. doi: 10.1172/JCI117796

Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules.

C J Chelen 1, Y Fang 1, G J Freeman 1, H Secrist 1, J D Marshall 1, P T Hwang 1, L R Frankel 1, R H DeKruyff 1, D T Umetsu 1
PMCID: PMC441485  PMID: 7533793

Abstract

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.

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Selected References

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