T-CELL RECEPTOR ALPHA/BETA-EXPRESSING DOUBLE-NEGATIVE (CD4-/CD8-) AND CD4+ T-HELPER CELLS IN HUMANS AUGMENT THE PRODUCTION OF PATHOGENIC ANTI-DNA AUTOANTIBODIES ASSOCIATED WITH LUPUS NEPHRITIS

  • 1 July 1989
    • journal article
    • research article
    • Vol. 143  (1) , 103-112
Abstract
It is generally accepted that human Th cells express the surface glycoproteins CD4 and .alpha./.beta.-chain heterodimer of the TCR whereas cytotoxic/suppressor cells are usually CD8+ and .alpha./.beta. TCR+. Another minor set of T cells found in the periphery are CD4-/CD8- (double negative) and express the .gamma.-.delta. TCR; these cells can manifest MHC-restricted or nonrestricted cytotoxicity but no helper function. Herein we describe the existence of an unusual Th population in the peripheral blood of humans that are CD4-/CD8- and .alpha./.beta. TCR+. These double-negative Th were markedly expanded in patients with the autoimmune disease SLE and along with CD4+ Th, they induced production of the pathogenic varient of anti-DNA autoantibodies that are IgG in class and cationic in charge. The cationic anti-DNA antibodies induced by the Th were markedly restricted in spectrotype indicating that an oligoclonal population of B cells were committed to produce the pathogenic autoantibodies in active lupus. IL-2-dependent T cell lines were also derived from the patients with active lupus nephritis but the majority of those T cell lines lacked pathogenic autoantibody-inducing capability. Only 4 out of 42 T cell lines from a lupus patient could induce the production of cationic IgG class anti-DNA auotantibodies. The phenotypes of the pathogenic autoantibody-inducing Th lines were similar to the Th subsets: CD4+, .alpha./.beta. TCR+ or CD4-/CD8-, .alpha./.beta. TCR+. These studies suggest that production of pathogenic autoantibodies in human lupus is mediated by mechanisms that are distinct from the generalized, nonspecific polyclonal B cell hyperactivity that leads to excessive production of natural autoantibodies.