CD8α is expressed by human monocytes and enhances FcγR-dependent responses.

Autor: Gibbings, Derrick J., Marcet-Palacios, Marcelo, Sekar, Yokananth, Ng, Marcus C.Y., Befus, A. Dean
Předmět:
Zdroj: BMC Immunology; 2007, Vol. 8, p12-16, 16p
Abstrakt: Background: CD8a enhances the responses of antigen-specific CTL activated through TCR through binding MHC class I, favoring lipid raft partitioning of TCR, and inducing intracellular signaling. CD8a is also found on dendritic cells and rat macrophages, but whether CD8a enhances responses of a partner receptor, like TCR, to activate these cells is not known. TCR and FcR, use analogous or occasionally interchangeable signaling mechanisms suggesting the possibility that CD8a co-activates FcR responses. Interestingly, CD8a+ monocytes are often associated with rat models of disease involving immune-complex deposition and FcR-mediated pathology, such as arthritis, glomerulonephritis, ischaemia, and tumors. While rat macrophages have been shown to express CD8a evidence for CD8a expression by mouse or human monocytes or macrophages was incomplete. Results: We detected CD8a, but not CD8ß on human monocytes and the monocytic cell line THP-1 by flow cytometry. Reactivity of anti-CD8a mAb with monocytes is at least partly independent of FcR as anti-CD8a mAb detect CD8a by western blot and inhibit binding of MHC class I tetramers. CD8a mRNA is also found in monocytes and THP-1 suggesting CD8a is synthesized by monocytes and not acquired from other CD8a+ cell types. Interestingly, CD8a from monocytes and blood T cells presented distinguishable patterns by 2-D electrophoresis. Anti-CD8a mAb alone did not activate monocyte TNF release. In comparison, TNF release by human monocytes stimulated in a FcR-dependent manner with immune-complexes was enhanced by inclusion of anti-CD8a mAb in immune-complexes. Conclusion: Human monocytes express CD8a. Co-engagement of CD8a and FcR enhances monocyte TNF release, suggesting FcR may be a novel partner receptor for CD8a on innate immune cells. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index