Elevated CTLA-4 expression on CD4 T cells from periodontitis patients stimulated with Porphyromonas gingivalis outer membrane antigen.
To characterize the T cell response to Porphyromonas gingivalis, we examined the expression of costimulatory molecules on T cells derived from adult periodontitis patients with high serum antibody titre to P. gingivalis. The expression of CD28, CTLA-4, CD40 ligand (CD40L) on CD4+ T cells was analysed by flow cytometry. IL-10 and transforming growth factor-beta (TGF-beta) mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and subsequent image analysis. Peripheral blood mononuclear cells (PBMC) derived from periodontitis patients showed higher proliferative responses to P. gingivalis outer membrane (OM) than those from healthy controls (P < 0.05). The percentage of CTLA-4+ cells within CD4+ T cells of patients was significantly higher than that of healthy controls after P. gingivalis OM stimulation (33.0% versus 11.9%, P < 0.01). There was no significant difference in the percentages of CD28+ cells and CD40L+ cells, and the percentage of CD40L+ cells was low in both groups even after stimulation. Stimulation of PBMC with P. gingivalis OM induced significantly higher IL-10 mRNA expression in periodontitis patients than in healthy controls (P < 0.05). The level of TGF-beta mRNA expression of patients tended to be higher than that of healthy controls, but there was no significant difference. To elucidate the functional role of CTLA-4, we further investigated the secondary proliferative response to P. gingivalis OM. Interestingly, P. gingivalis OM stimulation did not enhance antigen-specific secondary response. Anti-CTLA-4 MoAb had no effect on proliferation in the presence of P. gingivalis OM. CTLA-4Ig suppressed the proliferative response significantly (P < 0.01). These results suggest that T cell responses to P. gingivalis OM may be regulated by CTLA-4 that is expressed at the late phase of T cell activation, and, in part, immunosuppressive cytokines. Taken together, CTLA-4 may play a crucial role in the pathogenesis of chronic inflammatory periodontal disease.
Aoyagi
T
T
Department of Periodontology, Niigata University, Faculty of Dentistry, Niigata, Japan.
Yamazaki
K
K
Kabasawa-Katoh
Y
Y
Nakajima
T
T
Yamashita
N
N
Yoshie
H
H
Hara
K
K
D000069594:Abatacept; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D010518:Periodontitis / Q000276:immunology* / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001425:Bacterial Outer Membrane Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D012333:RNA, Messenger; D000069594:Abatacept