Cell-contact-dependent activation of CD4+T cells by adhesion molecules on synovial fibroblasts.
OBJECTIVE
To determine how cell-cell contact with synovial fibroblasts (SF) influence on the proliferation and cytokine production of CD4+T cells.


METHODS
Naïve CD4+T cells were cultured with SF from rheumatoid arthritis patients, stimulated by anti-CD3/28 antibody, and CD4+T cell proliferation and IFN-γ/IL-17 production were analyzed. To study the role of adhesion molecules, cell contact was blocked by transwell plate or anti-intracellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1(VCAM-1) antibody. To study the direct role of adhesion molecules for CD4+T cells, CD161+or CD161-naïve CD4+T cells were stimulated on plastic plates coated by recombinant ICAM-1 or VCAM-1, and the source of IFN-γ/IL-17 were analyzed.


RESULTS
SF enhanced naïve CD4+T cell proliferation and IFN-γ/IL-17 production in cell-contact and in part ICAM-1-/VCAM-1-dependent manner. Plate-coated ICAM-1 and VCAM-1 enhanced naïve CD4+T cell proliferation and IFN-γ production, while VCAM-1 efficiently promoting IL-17 production. CD161+naïve T cells upregulating LFA-1 and VLA-4 were the major source of IFN-γ/IL-17 upon interaction with ICAM-1/VCAM-1.


CONCLUSIONS
CD4+T cells rapidly expand and secrete IFN-γ/IL-17 upon cell-contact with SF via adhesion molecules. Interfering with ICAM-1-/VCAM-1 may be beneficial for inhibiting RA synovitis.
a Department of Rheumatology and Clinical Immunology.
Masato
M
Mori
b Department for the Control for Rheumatic Diseases.
Motomu
M
Hashimoto
a Department of Rheumatology and Clinical Immunology.
Takashi
T
Matsuo
b Department for the Control for Rheumatic Diseases.
Takao
T
Fujii
b Department for the Control for Rheumatic Diseases.
Moritoshi
M
Furu
b Department for the Control for Rheumatic Diseases.|c Department of Orthopedic Surgery , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
Hiromu
H
Ito
c Department of Orthopedic Surgery , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
Hiroyuki
H
Yoshitomi
d Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University , Kyoto , Japan.|e Immunology Research Unit , Astellas Pharma Inc., Drug Discovery Research , Tsukuba , Japan , and.
Jun
J
Hirose
f Department of Experimental Pathology , Institute for Frontier Medical Sciences, Kyoto University , Kyoto , Japan.
Yoshinaga
Y
Ito
a Department of Rheumatology and Clinical Immunology.
Shuji
S
Akizuki
a Department of Rheumatology and Clinical Immunology.
Ran
R
Nakashima
a Department of Rheumatology and Clinical Immunology.
Yoshitaka
Y
Imura
a Department of Rheumatology and Clinical Immunology.
Naoichiro
N
Yukawa
a Department of Rheumatology and Clinical Immunology.
Hajime
H
Yoshifuji
a Department of Rheumatology and Clinical Immunology.
Koichiro
K
Ohmura
a Department of Rheumatology and Clinical Immunology.
Tsuneyo
T
Mimori
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism* / Q000494:pharmacology
C508717:IL17A protein, human; D020381:Interleukin-17; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
CD161; CD4+ T cells; IFN-γ; IL-17; Intracellular adhesion molecule-1; Rheumatoid arthritis; Synovial fibroblasts; Vascular cell adhesion molecule-1