Characterization of the T-Cell Response to Polypropylene Mesh in Women With Complications

Polypropylene mesh has been widely used as surgical treatment for pelvic organ prolapse and stress urinary incontinence. Although mesh provides favorable functional and anatomic outcomes, its use has been limited by complications. The 2 most common of these are mesh exposure through the vaginal epithelium and pain. Accumulating evidence suggests that T lymphocytes play a critical role in the regulation of the host response to implanted mesh. The T-cell-mediated host cellular and tissue host responses include inflammation and healing of the surgical wound, as well as a foreign body reaction, which results in fibrous encapsulation of the mesh, effectively separating it from surrounding tissues. The T-cell response to polypropylene prolapse mesh and the role of T cells in vaginal mesh complications are not well characterized. The aims of this study were to define and characterize the T-cell response and to correlate the response to collagen deposition in fibrotic capsules in mesh tissue complexes removed for the separate complications of pain versus mesh exposure. The study was conducted at Magee Women's Hospital in Pittsburgh, Pa. Mesh-vagina tissue complexes were removed for the primary complaint of exposure or pain from42 women: 24 for exposure and 18 for pain. Control tissue was obtained from 21 patients who had an additional vaginal biopsy away from the site of mesh. Two predominant cytokines involved in the development of pathologic fibrosis were examined: transforming growth factor beta (TGF-beta 1) and connective tissue growth factor (CTGF). Tcells were examined by immunofluorescent labeling for cell surface markers CD4(+) (T helper), CD8(+) (cytotoxic), and foxp3 (T-regulatory cell). For fibrotic capsule quantification, frozen sections were stained with hematoxylin-eosin for gross morphologic condition and picrosirius red for collagen fiber analysis (red indicating thicker fibers and green thicker fibers). The content of collagen types I and III and the collagen III/I ratio were quantified using interrupted sodium dodecyl sulfate gel electrophoresis. Enzyme-linked immunosorbent assays were used to measure TGF-beta 1 and CTGF. The Student t tests, mixedeffects linear regression, and Spearman correlation coefficients were used for data analysis. There were no significant differences between groups in demographic data, except for body mass index, which was greater in the mesh exposure group (31.7 kg/m(2)) than in the pain group (28.2 kg/(2); P = 0.04). With immunofluorescent labeling, mesh-tissue complexes had a marked, but highly localized, foreign body response. In both pain and exposure groups, a teardrop-shaped cellular response was consistently observed that included the mesh capsule around each mesh fiber, with the T cells localized to the tip of the teardrop away from the mesh-tissue interface. Compared with tissue from control subjects, all 3 T-cell populations were significantly elevated in the exposure group: CD4 T helper (P < 0.001), CD8(+) (cytotoxic) (P = 0.034), and foxp3(+) (T regulatory) (P < 0.001). In the pain group, however, only CD4(+) (T-helper) (P < 0.001) and T-regulatory cells (P < 0.001) were increased; CD8(+) (cytotoxic) T cells were not different (P = 0.520). Characterization of the fibrous capsule using picrosirius red staining showed a greater area of green (thin) fibers in the exposure group (P = 0.025) and red (thick) fibers in the pain group (P < 0.001). The ratio of green/(yellow + orange + red) in the exposure group was greater (P = 0.005) compared with the pain group, indicating thinner fibers. Compared with control samples, analysis of collagen subtypes showed that collagen type I was increased by 35% in samples with mesh complications of exposure and pain (P = 0.043). There were strong correlations between the profibrosis CTGF and collagen types I and III in patients with pain (r = 0.833; P = 0.01), but not exposure (P > 0.65). These findings suggest that T cells play a critical role in the long-term host response to mesh and may be a central pathway leading to mesh complications. The complexity of the T-cell response to mesh relating to normal and abnormal host response may broaden our understanding of mesh biology and clinical outcomes.