REGULAR ARTICLES

Cell Research (2000), 10, 39--50

Isolation and characteristics of autoreactive T cells specific to aggrecan G1 domain from rheumatoid arthritis patients

LI Ning Li^1,*, Dong Qing ZHANG¹, Kuang Yan ZHOU¹, Annie CARTMAN², Jean Yves LEROUX², A Robin POOLE², Yi Ping ZHANG²

¹ Shanghai Institute of Immunology, Shagnhai Second Medical University, Shanghai 200025, China

² Joint Diseases Laboratory, Shriners Hospital, Department of Surgery, McGill University, Montreal, Canada

ABSTRACT
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 × 10^-6 in peripheral blood lymphocytes. We have also generated 15 G1-specific T lymphocyte lines from these pateints 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 ab T cell receptor. Two of them used gd 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-g 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 pateints. 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.

Key words:rG1-specific T cell lines, T cell receptor, cytokine profile, rheumatoid arthritis.

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