Published online before print April 28, 2009
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Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
1. Correspondence at current address: IBMP-CNRS UPR2357, 12 rue du general Zimmer, 67000 Strasbourg, France. E-mail: Derrick.gibbings{at}ibmp-ulp.u-strasbg.fr
CD8 and CD4 are expressed by several cell types that do not express TCR. These include DCs, macrophages, monocytes, and NK cells. CD8+ monocytes and macrophages are abundant at the site of pathology in many rat disease models, particularly those involving immune complex-mediated pathology. Indeed, in some disease models, CD8+ macrophages correlate with severity of pathology or directly cause pathology or tumor cell killing. Evidence suggests CD8 or CD4 can enhance Fc
R-dependent responses of human monocytes. Building on data that key components of TCR and Fc
R signaling can substitute one another efficiently, we postulate that CD4 and CD8 operate with Fc
R and potentially other receptors to enhance responses of T cells and various innate immune cells. Our model suggests CD8 on myeloid cells may contribute directly to tumor killing and tissue pathology by enhancing Fc
R responses. Moreover, the model suggests a role for CD8 in cross-presentation of antibody-associated antigen by DCs and a new mechanism to regulate TCR sensitivity.
Key Words: dendritic cells myeloid cells monocytes/macrophages natural killer cells TCR FcR gamma chain