Isolation and characteristics of autoreactive T cells specific to aggrecan G1 domain from rheumatoid arthritis patients.
Our previous work showed that the cartilage proteoglycan aggrecan could induce an erosive polyarthritis and spondylitis in BALB/c mice and the G1 globular domain of the aggrecan (G1) contained the arthritogenic region. To elucidate whether autoreactive T cells to G1 are expressed in rheumatoid arthritis patients, we analyzed the frequency of human G1-specific T cells in the peripheral blood of five rheumatoid arthritis patients and tried to establish G1-reactive T cell lines from these rheumatoid arthritis patients. The results showed that the G1-specific T cells in PBL were detectable at the range of 4.97 +/- 0.5 x 10(-6) in peripheral blood lymphocytes. We have also generated 15 G1-specific T lymphocyte lines from these patients with a standard split-well method. All these cells expressed fine specificity to human recombinant G1, but not to unrelated antigen. All the 15 lines expressed a pan-T cell marker and 13 of them selectively used the alphabeta T cell receptor. Two of them used gammadelta T cell receptor. The 13 of these T cell lines was CD4 positive. One line expressed CD8. One line expressed both CD4 and CD8. Moreover, 14 out of 15 lines expressed the Th-1 cytokine profile, characterized by interferon-gamma positivity and IL-4 negativity. No Th-2 type cell line was generated. These data provide strong evidence in favor of the presence of autoreactive T cells in the rheumatoid arthritis patients. What is the mechanism(s) that these autoreactive T cells attack self-target and whether these G1-specific, Th-1 type T cell lines can induce arthritis in immune deficiency mice are currently under investigation.
Li
N L
NL
Shanghai Institute of Immunology, Shanghai Second Medical University, China.
Zhang
D Q
DQ
Zhou
K Y
KY
Cartman
A
A
Leroux
J Y
JY
Poole
A R
AR
Zhang
Y P
YP
D000328:Adult; D000368:Aged; D053674:Aggrecans; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D016326:Extracellular Matrix Proteins; D006801:Humans; D037181:Lectins, C-Type; D008875:Middle Aged; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D011948:Receptors, Antigen, T-Cell