Adoptive transfer of cloned T helper cells ameliorates periodontal disease in nude rats

Abstract

We have previously described a T helper cell 2-type clone, A3, of rat T cells that provides help for antibody production to Actinobacillus actinomycetemcomitans in vitro and in vivo in normal (euthymic) isogeneic Rowett strain recipient rats. Adoptive transfer of this T helper cell clone to euthymic rats also protects them from periodontal bone loss induced by oral infection with A. actinomycetemcomitans. In the present study, to assess the cell requirement for protection, A3 clone T lymphocytes (10(6)) or naive lymph node (6 x 10(4)) T cells, or A3 plus naive lymph node T cells (6 x 10(4)) were adoptively transferred to groups (n = 7-9) of 30-day-old Rowett athymic nude (rnu/rnu) rats. All recipients were also immunized (intraperitoneally) with 10(7) killed A. actinomycetemcomitans on the day of T cell transfer and orally infected with these bacteria on each of the next 5 days. Recipients of the combined A3+lymph node T cell transfer showed significantly increased serum immunoglobulin G (IgG) and IgM antibody to A. actinomycetemcomitans and in vitro proliferation of spleen lymphocytes to A. actinomycetemcomitans as antigen compared with nude animals receiving lymph node T cells only. Although other possibilities are discussed, we inferred that these differences might be due to successful population of the congenitally athymic rats by A3 clone cells given with a small number of normal autologous naive lymph node T cells. The result of this co-transfer of naive T cells with the A3 clone cells seemed to be greatly increased antibody production and protection from periodontal bone loss.

Bacterial-Responsive B Lymphocytes Induce Periodontal Bone Resorption

“…It is not clear whether this difference indicates that B cells can contribute more extensively to bone resorption than T cells in the lesions. In our adoptive transfer studies Th2 cells ameliorated bone resorption and resulted in marked increased in Ab (12,28). In the more recent studies several Th1 Ag-specific clones gave rise to significant bone resorption that could be ablated with CTLA4-Ig and OPG-Fc (13,22).…”

Th1 biased response to a novel Porphyromonas gingivalis protein aggravates bone resorption caused by this oral pathogen

“…We and others have shown that infection with live P. gingivalis predominantly elicits a Th1-type response in experimental animals and in humans [15]. In addition, adoptive transfer experiments have indicated an active role for Th1 cytokines in periodontal disease exacerbation, and some studies have shown that Th2 cytokines may be protective [9,16]. However, other studies suggest that this association is not consistently observed [17,18,19].…”

Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection

“…A. actinomycetemcomitans infection is usually accompanied by local and systemic antigen-specific immune responses (18)(19). Earlier studies demonstrated altered CD4 + /CD8 + T-cell ratios and autologous mixed lymphocyte reactions in LJP patients (20,21) and the ability of T helper cells to home to periodontal tissues in rat and mouse models of periodontitis (22)(23)(24). Further, we have previously demonstrated that A. actinomycetemcomitans infection in NOD/SCID mice engrafted with human peripheral blood leukocytes (HuPBLs) leads to periodontal inflammation characterized by the infiltration of CD4 + T cells, CD8 + T cells, CD20 + B cells, and Mac1 + macrophages into the fibrous connective tissues adjacent to the periodontal pockets (24).…”