title: Decreased T cell response to anti-CD2 in systemic lupus erythematosus and reversal by anti-CD28: evidence for impaired T cell-accessory cell interaction.
abstract: OBJECTIVE
  To assess the ability of T cells from patients with systemic lupus erythematosus (SLE) to respond to a mitogenic combination of anti-CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect.
  
  
  METHODS
  Peripheral blood mononuclear cell (PBMC) populations from individuals with SLE and paired controls were stimulated in vitro with anti-CD2, and the proliferative response was compared with that evoked by stimulation with phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb.
  
  
  RESULTS
  The proliferative response to anti-CD2 was decreased to a greater extent than was the response to anti-CD3 or PHA in SLE patients. This defect was found in approximately one-half of the patients examined, was not associated with disease activity, and was maintained upon repeated testing. Since either monocytes or resting B cells can serve as accessory cells for T cells following activation by anti-CD2, we examined the T cell response after depletion of adherent cells. In approximately two-thirds of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from normal donors corrected the defect. The addition to PBMC of anti-CD28, but not of a neutralizing antibody to interleukin-10, largely reversed the anti-CD2 proliferative defect. Significantly fewer CD8+ T cells expressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells.
  
  
  CONCLUSIONS
  This study provides evidence that some functional T cell defects in SLE may be due, at least in part, to decreased CD28-mediated costimulatory activity following the interaction of T cells with conventional accessory cells.
authors.affiliation: University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Horwitz
authors.forename: F L
authors.initials: FL
authors.lastname: Tang
authors.forename: M M
authors.initials: MM
authors.lastname: Stimmler
authors.forename: A
authors.initials: A
authors.lastname: Oki
authors.forename: J D
authors.initials: JD
authors.lastname: Gray
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000166:cytology; D018801:CD2 Antigens / Q000276:immunology*; D018106:CD28 Antigens / Q000502:physiology; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication; D002455:Cell Division / Q000276:immunology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D018106:CD28 Antigens; D016753:Interleukin-10