T Regulatory Cells and TH17 Cells in Peri–Silicone Implant Capsular Fibrosis

• DOI: 10.1097/prs.0b013e31823aeacf
• Publication Date: 2012-01-28T06:58:16Z
• Authors: Dolores Wolfram; Evelyn Rabensteiner; Cecilia Grundtman; Günther Böck; Christina Mayerl; Walther Parson; Giovanni Almanzar; Carlo Hasenöhrl; Hildegunde Piza-K...; Georg Wick
• Keywords: Adult; Breast Implants; Middle Aged; Sodium Chloride; Fibrosis; T-Lymphocytes, Regulatory; 3. Good health; Silicone Gels; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Implant Capsular Contracture; Humans; Th17 Cells; Female; Breast

The authors investigated the immunological mechanisms underlying extensive peri-silicone implant capsule formation, one of the most frequent postoperative complications in patients receiving silicone mammary implants.The authors studied immune response activation by phenotypic and functional characterization of lymphocytes accumulated within this tissue. Intracapsular lymphoid cells and autologous peripheral blood mononuclear cells were isolated and analyzed by flow cytometry. The proportion of T regulatory cells (CD4+ CD25(high) Foxp3+ CD127), the cytokine profiles, and the T cell receptor repertoire of these cells were examined. Intracapsular T regulatory cells were then further analyzed by immunohistochemistry and functional suppression assays.In comparison with peripheral blood, the cellular composition of intracapsular lymphocytes showed a predominance of CD4+ cells. Intracapsular T cells predominantly produced interleukin-17, interleukin-6, interleukin-8, transforming growth factor-β1, and interferon-γ, suggesting a TH1/TH17-weighted local immune response. Intracapsular T cells displayed a restricted T cell receptor α/β repertoire. The intact suppressive potential of T regulatory cells was demonstrated in crossover experiments with activated peripheral T cells. They did not, however, suppress intracapsular T cells. Interestingly, ratios of intracapsular T regulatory cells were inversely proportional to the clinical degree of capsular fibrosis.The authors' results indicate that silicone implants trigger a specific, antigen-driven local immune response through activated TH1/TH17 cells, suggesting that ensuing fibrosis is promoted by the production of profibrotic cytokines as a consequence of faltering function of local T regulatory cells.