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 language||English (US)|
|Number of pages||10|
|Journal||Journal of Immunology|
|State||Published - 1989|
ASJC Scopus subject areas
- Immunology and Allergy