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Pathogenic Anti-DNA Autoantibody-Inducing T Helper Cell Lines from Patients with Active Lupus Nephritis: Isolation of CD4-8- T Helper Cell Lines That Express the γδ T-Cell Antigen Receptor
Sumati Rajagopalan, Tracy Zordan, George C. Tsokos and Syamal K. Datta
Proceedings of the National Academy of Sciences of the United States of America
Vol. 87, No. 18 (Sep., 1990), pp. 7020-7024
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2355155
Page Count: 5
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The antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. In spite of this obstacle, we show that T helper (Th) cell lines that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (≈ 15%) of these lines had the ability to selectively augment the production of pathogenic anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the αβ T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the αβ TCR and 7 expressing the γδ TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients' B cells were involved in stimulating an autoreactive proliferation of the γδ Th cells. These studies demonstrate a novel helper activity of certain γδ T cells in a spontaneous autoimmune response
Proceedings of the National Academy of Sciences of the United States of America © 1990 National Academy of Sciences