title: Immunohistochemical analysis of lymphocyte subpopulations in cyclosporin A-induced gingival overgrowth.
abstract: BACKGROUND
  Cyclosporin A (CsA) is an immunosuppressive agent that is known to induce gingival overgrowth (GO). Pharmacological, genetic, immunologic, and inflammatory factors seem to be involved in the complex pathogenesis of drug-induced GO. Lymphocyte subpopulations in human gingival connective tissue have been implicated in the pathogenesis of inflammatory periodontal diseases. One purpose of this study was to quantify CD4, CD8-, CD57-, and epithelial membrane antigen (EMA)-positive cells in the gingiva of renal transplant recipients treated with CsA, and compare them to findings in healthy controls. A second aim was to correlate cell numbers with clinical findings.
  
  
  METHODS
  The study included 19 kidney recipients who were taking CsA and had significant GO (CsAGO+), 13 recipients who were taking CsA but showed no GO (CsAGO-), and 14 systemically healthy individuals with gingivitis (C). Sections from gingival biopsies were incubated with monoclonal antibodies for CD4, CD8, EMA, and CD57, and then analyzed using the avidin-biotin complex method. In each specimen, the mononuclear cell types were quantified and their distribution was evaluated in 3 separate tissue zones: S = subepithelial connective tissue beneath the sulcular epithelium; O = subepithelial connective tissue beneath the oral epithelium; and M = middle connective tissue.
  
  
  RESULTS
  There were no significant differences among the groups with respect to the numbers of CD4+ and CD8+ cells in each of the 3 zones (P >0.05). In zone S, the CsAGO+ group had significantly more EMA-positive cells than either the C or CsAGO- groups (P <0.05). There were significant differences among the groups regarding numbers of CD57+ (natural killer) cells in zone M, with the lowest cell numbers in the CsAGO+ patients (P<0.05).
  
  
  CONCLUSIONS
  The results showed that low numbers of natural killer cells are important in the expression of plaque-induced inflammatory changes in CsA-associated GO. It appears that these cells may influence the drug's ability to induce proliferative activity.
authors.affiliation: Department of Periodontology, Başkent University Faculty of Dentistry, Ankara, Turkey.
authors.forename: Sule
authors.initials: S
authors.lastname: Bulut
authors.forename: Emine E
authors.initials: EE
authors.lastname: Alaaddinoglu
authors.forename: Banu
authors.initials: B
authors.lastname: Bilezikçi
authors.forename: Beyhan
authors.initials: B
authors.lastname: Demirhan
authors.forename: Gokhan
authors.initials: G
authors.lastname: Moray
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000145:classification; D018959:CD57 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000145:classification; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D016572:Cyclosporine / Q000009:adverse effects*; D003774:Dental Plaque Index; D005260:Female; D005881:Gingiva / Q000187:drug effects / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000473:pathology*; D005891:Gingivitis / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000473:pathology; D007694:Killer Cells, Natural / Q000145:classification; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000145:classification*; D008297:Male; D018396:Mucin-1 / Q000032:analysis; D010512:Periodontal Index; D010950:Plasma Cells / Q000145:classification; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
chemical_list: D000911:Antibodies, Monoclonal; D018959:CD57 Antigens; D007166:Immunosuppressive Agents; D018396:Mucin-1; D016572:Cyclosporine