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 gamma delta T-cell antigen receptor.
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 (approximately 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 alpha beta T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the alpha beta TCR and 7 expressing the gamma delta 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 gamma delta Th cells. These studies demonstrate a novel helper activity of certain gamma delta T cells in a spontaneous autoimmune response.
Rajagopalan
S
S
Department of Medicine, New England Medical Center, Boston, MA 02111.
Zordan
T
T
Tsokos
G C
GC
Datta
S K
SK
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001323:Autoantibodies / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens; D002460:Cell Line; D004247:DNA / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D006360:Heat-Shock Proteins; D011948:Receptors, Antigen, T-Cell; D004247:DNA