Binding of Porphyromonas gingivalis gingipains to human CD4(+) T cells preferentially down-regulates surface CD2 and CD4 with little affect on co-stimulatory molecule expression.
The role of Porphyromonas gingivalis cysteine proteinases (gingipains) in the evasion of host cell-mediated immunity has not been fully determined. In this study, modulation by gingipains of accessory and co-stimulatory molecule expression on human CD4(+) T cells was evaluated. Arg-gingipain rather than Lys-gingipain binds to resting CD4(+) T cells in the presence of serum. The constitutive expression of CD28 on T cells was slightly up-regulated following challenge with gingipains, whereas CD45 and CD3 were not affected. Binding of anti-CD2 and anti-CD4 monoclonal antibodies (mAbs) was reduced after challenge of T cells with gingipains, but restored to 50 and 100%, respectively, of control levels, after 48h of incubation in medium depleted of gingipains. The induced expression, by anti-CD3 mAb, of CTLA-4, CD25, and CD40 ligand (CD40L) was decreased following incubation of T cells with gingipains which also led to decreased response to anti-CD3 and anti-CD28 mAbs as shown by reduction of interleukin-2 (IL-2) production. Cumulatively, these results indicate that activated gingipains attach to T cells and preferentially cleave CD2 and CD4 molecules, with potential to impair T cell responses at periodontal sites.
Yun
Peter L W
PL
Institute of Dental Research, Westmead Millennium Institute and Centre for Oral Health, P. O. Box 533 Wentworthville, Sydney, NSW, Australia. plwyun@yahoo.com
Decarlo
Arthur A
AA
Chapple
Cheryl C
CC
Collyer
Charles A
CA
Hunter
Neil
N
D018829:Adhesins, Bacterial; D000818:Animals; D018801:CD2 Antigens / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005786:Gene Expression Regulation; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D016966:Porphyromonas gingivalis / Q000276:immunology*
D018829:Adhesins, Bacterial; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D007376:Interleukin-2; D017493:Leukocyte Common Antigens; D003546:Cysteine Endopeptidases