title: Restricted and shared patterns of TCR beta-chain gene expression in silicone breast implant capsules and remote sites of tissue inflammation.
abstract: Silicone breast implants (SBI) induce formation of a periprosthetic, often inflammatory, fibrovascular neo-tissue called a capsule. Histopathology of explanted capsules varies from densely fibrotic, acellular specimens to those showing intense inflammation with activated macrophages, multinucleated giant cells, and lymphocytic infiltrates. It has been proposed that capsule-infiltrating lymphocytes comprise a secondary, bystander component of an otherwise benign foreign body response in women with SBIs. In symptomatic women with SBIs, however, the relationship of capsular inflammation to inflammation in other remote tissues remains unclear. In the present study, we utilized a combination of TCR beta-chain CDR3 spectratyping and DNA sequence analysis to assess the clonal heterogeneity of T cells infiltrating SBI capsules and remote, inflammatory tissues. TCR CDR3 fragment analysis of 22 distinct beta variable (BV) gene families revealed heterogeneous patterns of T cell infiltration in patients' capsules. In some cases, however, TCR BV transcripts exhibiting restricted clonality with shared CDR3 lengths were detected in left and right SBI capsules and other inflammatory tissues. DNA sequence analysis of shared, size-restricted CDR3 fragments confirmed that certain TCR BV transcripts isolated from left and right SBI capsules and multiple, extracapsular tissues had identical amino acid sequences within the CDR3 antigen binding domain. These data suggest that shared, antigen-driven T cell responses may contribute to chronic inflammation in SBI capsules as well as systemic sites of tissue injury.
authors.affiliation: Laboratory of Molecular and Developmental Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: O'Hanlon
authors.forename: O J
authors.initials: OJ
authors.lastname: Lawless
authors.forename: W E
authors.initials: WE
authors.lastname: Katzin
authors.forename: L J
authors.initials: LJ
authors.lastname: Feng
authors.forename: F W
authors.initials: FW
authors.lastname: Miller
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001940:Breast / Q000473:pathology; D018427:Breast Implants / Q000009:adverse effects*; D002999:Clone Cells; D022801:Complementarity Determining Regions; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007150:Immunohistochemistry; D008413:Mastitis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D020034:Silicone Gels / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020034:Silicone Gels; D004247:DNA