Correlation of CD4⁺ CD25⁺ Foxp3⁺ Treg with the recovery of joint function after total knee replacement in rats with osteoarthritis.

In this study, we observed changes in CD4(+) CD25(+) Foxp3(+) Treg expression in rats with osteoarthritis (OA) to explore the role that CD4(+) CD25(+) Foxp3(+) Treg plays in the decline in the condition of OA rats. Thirty rats were randomly divided into 2 groups equally and OA was induced in rats in the model group by injection of papain and l-cysteine into the right knee joint. Cartilage lesions were scored by the modified Mankin scale; pulmonary function was assessed by spirometry; interleukin (IL)-17 and IL-4 levels were evaluated by the enzyme-linked immunosorbent assay; and the levels of CD4(+) CD25(+) Foxp3(+) Treg in peripheral blood were measured by flow cytometry. The left knee joints of the model rats appeared palpable swelling and osteophytes, while the body weight, heart and lung function of these rats decreased. The serum IL-4 level was lower, whereas the serum IL-17 level was higher in the model group (P < 0.05). The peripheral blood CD4(+) CD25(+) Foxp3(+) Treg of CD4(+)T cells was significantly lower. Correlation of the changes in the levels of IL-4, IL-17, and Treg suggests that the underlying mechanism may be a reduction of the regulatory effect of Treg. The specific mechanism still requires further study.

The MAP kinases are differently utilized by CD28 and CD2 adhesion pathways in superantigen-activated Jurkat T cells.

To mimic the two-signal requirements for T cell activation mediated by ligands, we exposed the superantigens SEA or SEE (signal 1) to T cells incubated with HLA-DR/LFA-3 or HLA-DR/B7-1-CHO transfected cells (signal 2). LFA-3 costimulation was able to induce T cell proliferation as well as IFN-gamma and IL-4 production at similar levels as in cells induced by B7-1. Analysis of the CD28RE of the IL-2 promoter showed specific transcription factor recruitment at the CD28RE element upon induction by B7-1/SEE. Further functional studies with an IL-2 enhancer-promoter carrying either wild type or mutated versions of the CD28RE site revealed that this element is necessary for full activation upon B7-1 costimulation. While both CD28/B7-1 and CD2/LFA-3 costimulation resulted in the up-regulation of IL-4 and IFN-gamma promoters, IL-2 promoter activity and production of IL-2 were only seen after B7-1 costimulation. However, contrary to what has been previously proposed, we show that costimulation with either B7-1 or LFA-3 further enhanced the ERK-2 activity and strongly activated the p38 MAPK pathway, but only B7-1 costimulation induced high levels of JNK-1 activity. These data suggest that the differential effect of CD28 vs. CD2 can be related to the difference in the ability of the two pathways to induce JNK-1 activity.