Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

A Modulatory Effect of CD14+CD16++ Monocytes on CD14++Cd16- Monocytes: A Possible Explanation of Monocyte Alterations in Systemic Lupus Erythematosus.

Abstract

Objective. In different chronic inflammatory processes, both the proportion and numbers of monocyte subsets are altered. In systemic lupus erythematosus (SLE), this has not been clearly determined. The monocyte subpopulations in patients with SLE, other autoimmune diseases (OAD) and Healthy Controls (HCs) were evaluated. The effects of non-classical monocytes and apoptotic cells (ACs) on the differentiation and function of CD14++CD16- monocytes were also studied. Methods. The monocyte subpopulations from the blood samples of SLE (88) and OAD (37) patients and HCs (61) were tested by FACS. To evaluate the effect of CD14+CD16++ monocytes and ACs on the differentiation of CD14++CD16- monocytes, we developed a co-culture model of highly purified sorted monocyte subpopulations, which were reconstituted with defined proportions of CD14++CD16- and CD14+CD16++ monocytes in the presence or absence of ACs. After the differentiation into macrophages, CD3+ lymphocytes were added, and the proliferating and CD3+IFN-γ+ cells were evaluated. A cytokine bead array panel was used to test the co-culture supernatants. Results. Our results demonstrate that in active SLE (aSLE) patients, there was a reduction in CD14+CD16++ monocytes. Monocytes from SLE patients have a decreased expression of HLA-DR and ability to bind and phagocytize ACs. In HCs, but not in SLE patients, macrophages derived from CD14+CD16++ monocytes reduced T cell proliferation and proliferating CD3+IFN γ+ cells and increased the accumulation of the TNF-α, IL-10 and IL-1β. Conclusion. Our findings evidenced that, a population reduced and non-functional in SLE patients, CD14+CD16++ monocytes, has modulatory effects on the CD14++CD16- monocytes and T cells