Particulate poly(methyl methacrylate) could stimulate proinflammatory CD4 T cell responses in a monocyte-dependent manner, and directly mediate cell death

Abstract

Poly(methyl methacrylate) (PMMA) is a synthetic polymer that has been widely used in various medical implants. Traditionally considered a biologically inert material, it is now understood that PMMA may have proinflammatory properties. Here, we present a proof-of-concept study of the effect of PMMA on CD4 T cells. Using particulate PMMA, a material that resembled wear debris in orthopedic implants, to stimulate whole peripheral blood mononuclear cells, we found that the expression of IFNgamma, IL-4, IL-17, and TGFbeta could all be upregulated in CD4 T cells in a manner that was dependent on the dose of particulate PMMA. Furthermore, compared to direct anti-CD3/CD28 stimulation, PMMA preferentially stimulated the expression of IFNgamma and IL-17 but not the expression of IL-4 or TGFbeta. Interestingly, the presence of autologous monocytes was required, since PMMA had no stimulatory effect on isolated CD4 T cells. We further demonstrated that direct monocyte-CD4 T cell contact was required, and the costimulatory molecules CD80 and CD86 were involved for the optimal stimulation of CD4 T cells. PMMA also directly mediated the death of CD4 T cells in a manner that was dependent on dose but independent of the presence of monocytes. Overall, our study revealed that PMMA could induce CD4 T cell death, and also could result in CD4 T cell activation with a preference toward proinflammatory responses in a monocyte-dependent manner.