CD8 alpha is expressed by human monocytes and enhances Fc gamma R-dependent responses.
BACKGROUND
CD8 alpha 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. CD8 alpha is also found on dendritic cells and rat macrophages, but whether CD8 alpha 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 CD8 alpha co-activates FcR responses. Interestingly, CD8 alpha+ 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 CD8 alpha evidence for CD8 alpha expression by mouse or human monocytes or macrophages was incomplete.


RESULTS
We detected CD8 alpha, but not CD8 beta on human monocytes and the monocytic cell line THP-1 by flow cytometry. Reactivity of anti-CD8 alpha mAb with monocytes is at least partly independent of FcR as anti-CD8 alpha mAb detect CD8 alpha by western blot and inhibit binding of MHC class I tetramers. CD8 alpha mRNA is also found in monocytes and THP-1 suggesting CD8 alpha is synthesized by monocytes and not acquired from other CD8 alpha+ cell types. Interestingly, CD8 alpha from monocytes and blood T cells presented distinguishable patterns by 2-D electrophoresis. Anti-CD8 alpha 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-CD8 alpha mAb in immune-complexes.


CONCLUSIONS
Human monocytes express CD8 alpha. Co-engagement of CD8 alpha and FcR enhances monocyte TNF release, suggesting FcR may be a novel partner receptor for CD8 alpha on innate immune cells.
Pulmonary Research Group, Division of Pulmonary Medicine, Department of Medicine, University of Alberta, Canada. gibbings@ualberta.ca
Derrick J
DJ
Gibbings
Marcelo
M
Marcet-Palacios
Yokananth
Y
Sekar
Marcus C Y
MC
Ng
A Dean
AD
Befus
D000936:Antigen-Antibody Complex / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000936:Antigen-Antibody Complex; D016827:CD8 Antigens; C431698:CD8alpha antigen; D015395:Histocompatibility Antigens Class I; D017452:Receptors, IgG; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha