CD101 expression and function in normal and rheumatoid arthritis-affected human T cells and monocytes/macrophages.

Objective. It was recently reported that CD101 surface expression discriminates potency among CD4+CD25+ FoxP3+ regulatory T cells in the mouse. We investigated whether CD 101 may also have a role in the suppressor function of regulatory T cells in humans given that the latter population may affect the autoimmune response in patients with rheumatoid arthritis (RA). Methods. Sorted T cells and monocyte/macrophage cell populations were analyzed by flow cytometry using conjugated antibodies specific for cell-surface markers. T cell proliferation assays were conducted by [H-3]thymidine incorporation and CD8(high) cytotoxicity measurements by Cyto-Scan-LDH cytotoxicity assays. ELISA were used to measure cytokines in cell culture super-natants and Western blotting was performed for profiling mitogen-activated protein (MAP) kinase activation using specific antiphospholipid antibodies. Results. CD101 expression coincided with PMA-induced monocyte/leukocyte lineage differentiation. CD85(high)CD101-T cells exhibited greater cytotoxic activity than CD8(high)CD101+ T cells, while no difference was observed between CD4CD25(high)CD101+ and CD4CD25(high)CD101- Treg inhibitory activity through responder T cells. LPS-induced proinflammatory cytokine production and p38 MAP kinase activation were made possible by ligation of CD101 with an anti-CD101 antibody F(ab')(2) fragment. Conclusion. These results suggested a modulatory/coregulatory function of CD101 in the human immune system, in contrast to murine models, in which CD101 surface expression discriminates potency among FoxP3+ regulatory T cells. Cytotoxic CD8(high)CD101+ T cells were markedly less cytotoxic than CD8(high) T cells negative for the CD 101 antigen and were conspicuously downregulated in patients with RA, suggesting a possible role for CD 101 expression and function in the control of certain manifestations of RA pathology. (First Release Dec 15 2010; J Rheumatol 2011;38:419-28; doi:10.3899/jrheum.100676)