Characterization of in vivo mutated T cell clones from patients with systemic lupus erythematosus

Stamatios Theocharis, Petros P. Sfikakis, Robert N. Lipnick, Gary Klipple, Alfred D. Steinberg, George C. Tsokos

Research output: Contribution to journalArticle

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Abstract

Patients with systemic lupus erythematosus (SLE) have increased percentages of activated T cells and increased numbers of cells with mutations in their hypoxanthine-guanine phosphoribosyltransferase (hprt) gene, as Judged by growth in the presence of 6-thioguanine. To study the relevance of these mutant T cells to disease pathogenesis, we have assessed the phenotype and functional capabilities of such cells from 21 patients with SLE who never had received cytotoxic drugs. The frequency of T cells with mutations in hprt in the blood of these patients ranged from normal to 25 times normal (mean ± SEM [21.1 ± 6.1] x 10-6 versus [4.8 ± 0.81 x 10-6, in 15 age-matched normal individuals, P < 0.001) and correlated significantly with disease duration. CD4+ and CD8+ phenotypes were comparable among mutated and nonmutated clones from both patients and normals. Although the frequency of CD3+CD4-CD8- cells was low, it was increased among SLE-derived T cells (mutated and wild-type) compared with clones derived from normals (5% for SLE vs 1% for normals). A substantial percentage of all clones were able to help autologous B cells to produce anti-ssDNA, 11 of 68 (16%) selected clones and 3 of 28 (11%) nonselected clones. Help for autoantibody production was confined to CD4+ SLE-derived T cell clones. It could be blocked using an anti-HLA-DR mAb, suggesting that classical cognate help was operative. This represents the first estimate of the frequency of T cells able to drive autoantibody production in SLE.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalClinical Immunology and Immunopathology
Volume74
Issue number2
DOIs
StatePublished - Jan 1 1995

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Systemic Lupus Erythematosus
Clone Cells
T-Lymphocytes
Hypoxanthine Phosphoribosyltransferase
Autoantibodies
Phenotype
Thioguanine
Mutation
HLA-DR Antigens
B-Lymphocytes
Cell Count
Growth
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

Cite this

Characterization of in vivo mutated T cell clones from patients with systemic lupus erythematosus. / Theocharis, Stamatios; Sfikakis, Petros P.; Lipnick, Robert N.; Klipple, Gary; Steinberg, Alfred D.; Tsokos, George C.

In: Clinical Immunology and Immunopathology, Vol. 74, No. 2, 01.01.1995, p. 135-142.

Research output: Contribution to journalArticle

Theocharis, Stamatios ; Sfikakis, Petros P. ; Lipnick, Robert N. ; Klipple, Gary ; Steinberg, Alfred D. ; Tsokos, George C. / Characterization of in vivo mutated T cell clones from patients with systemic lupus erythematosus. In: Clinical Immunology and Immunopathology. 1995 ; Vol. 74, No. 2. pp. 135-142.
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