The foreign body reaction in T-cell-deficient mice.

ABSTRACT

The role(s) of T lymphocytes in the foreign body response has not been thoroughly elucidated. Lymphocytes are known to augment macrophage adhesion and fusion in vitro. Furthermore, T lymphocytes are a possible source of the cytokines, IL-4 and IL-13, which induce macrophage fusion. In this study, we used BALB/c mice and BALB/c (nu/nu) nude mice to investigate foreign body giant cell (FBGC) formation in a T-cell-deficient setting. Mice were implanted with Elasthane 80A (PEU), silicone rubber (SR), or poly(ethylene terephthalate) (PET) for 7, 14, or 21 days using the cage implant system. Exudate cells and IL-4 and IL-13 levels in exudate supernatants were analyzed by flow cytometry and a multiplex immunoassay, respectively, at Days 7, 14, and 21. Macrophage adhesion and fusion on material surfaces were analyzed using optical microscopy. T-cell-deficient mice had lower total leukocyte concentrations at the biomaterial implant site at all time points. Adherent cell density was comparable between normal and T-cell-deficient mice except in the PEU group at Day 21. However, percent fusion, average nuclei per FBGC, and FBGC morphology were comparable between normal and T-cell-deficient mice. IL-4 was not detected in any sample, but IL-13 levels were also comparable between normal and T-cell-deficient mice indicating Th2-polarized T-cells are not the sole source of this cytokine. We have shown that there are pathways that do not require thymus-matured T lymphocytes, which lead to a normal foreign body response to biomaterials in a murine model.