CLONING, CHARACTERIZATION, AND ANTIGEN-SPECIFICITY OF T-LYMPHOCYTE SUBSETS EXTRACTED FROM GINGIVAL TISSUE OF CHRONIC ADULT PERIODONTITIS PATIENTS

Chronic periodontitis is characterized by dense infiltrations of B aci d T lymphocytes within the gingival connective tissue. Distinct anaero bic gram-negative bacteria as well as autoimmunity to collagen have be en reported to play a role in the etiology and the pathogenesis of thi s disease. Here we describe the cloning and characterization of CD4(+) and CD8(+). T lymphocytes isolated from inflamed gingival tissue obta ined from four patients with chronic periodontitis. Clones were raised with phytohemagglutinin and interleukin-2 and tested for proliferatio n in response to whole-cell antigens of Porphyromonas gingivalis, Prev otella intermedia, Actinobacillus actinomycetemcomitans, human collage n type I, and two bacterial heat shock proteins. CD4(+) T-cell clones reactive with collagen type I were obtained from all four patients. Ei ghty percent of these clones had phenotypes resembling the mouse type 2 T helper (Th) phenotype, i.e., they produced high levels of interleu kin-4 and low levels of gamma interferon. No collagen-type-I-reactive CD8(+) clones were obtained. Bacterial-antigen-reactive CD4(+) and/or CD8(+) T-cell clones were also obtained from each patient, and the maj ority of the clones showed a Th0-like cytokine pattern and produced eq ual amounts of interleukin-4 and gamma interferon. Although most clone s were reactive with P. intermedia, it seems that the immune response is not strictly directed against this particular microorganism, as clo nes reactive with one of the other bacteria were also obtained from tw o patients. We propose that collagen-specific CD4(+). Th2-like T cells contribute to the chronicity of periodontitis but that their modes of activation might be controlled by Th0-like T cells specific for perio dontitis-associated bacteria.