Immunohistochemical analysis of lymphocyte subpopulations in cyclosporin A-induced gingival overgrowth

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.

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.

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).

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.