T cell receptor α/β expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis

S. Shivakumar, G. C. Tsokos, S. K. Datta

Research output: Contribution to journalArticlepeer-review

317 Scopus citations


It is generally accepted that human Th cells express the surface glycoproteins CD4 and α/β-chain heterodimer of the TCR whereas cytotoxic/suppressor cells are usually CD8+ and α/β TCR+. Another minor set of T cells found in the periphery are CD4-/CD8- (double negative) and express the γ/δ 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 α/β 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 variety of anti-DNA autoantibodies that are IgG in class and cationic in change. 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 acute 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 the 42 T cell lines from a lupus patient could induce the production of cationic IgG class anti-DNA autoantibodies. The phenotypes of the pathogenic autoantibody-inducing Th lines were similar to the Th subsets: CD4+, α/β TCR+ or CD4-/CD8-, α/β 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.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalJournal of Immunology
Issue number1
StatePublished - 1989

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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