Th1-like cytokine production profile and individual specific alterations in TCRBV-gene usage of T cells from newly diagnosed type 1 diabetes patients after stimulation with beta-cell antigens

J Autoimmun. 1997 Dec;10(6):589-98. doi: 10.1006/jaut.1997.0167.


In order to study cytokine production profile (IFN-gamma, IL-4 and TNF-alpha) and TCRBV-gene usage of peripheral autoreactive T cells from IDDM patients, we have generated antigen-specific T cell lines with either tetanus toxoid, insulinoma membranes or a single beta-cell protein, recombinant ICA69, which has been shown to be a target of both autoantibodies and T cells in IDDM. By semi-quantitative polymerase chain reaction (PCR) analysis, we have determined the composition of the T cell receptor repertoire of these T cell lines and compared this with the general peripheral repertoire. T cell responses against beta-cell antigens and tetanus toxoid (TT) were shown to be associated with IFN-gamma and TNF-alpha production, suggestive of a Th1-like phenotype of the T-cell lines. The production of IFN-gamma was significantly higher in T-cell lines generated with ISG compared to those generated with TT. The cytokine production profiles of the T-cell lines generated with ICA69 did not provide an obvious explanation for the inverse relation between cellular and humoral responses to this protein observed earlier. Upon stimulation with beta-cell antigens, outgrowth of T cells using a restricted set of TCRBV elements was observed in newly diagnosed IDDM patients. However, this skewing in TCRBV-gene expression was patient-specific rather than antigen-associated, since the T-cell repertoire that is used for the recognition of these antigens was, overall, heterogeneous.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens / immunology
  • Antigens / pharmacology*
  • Autoantigens / pharmacology
  • Child
  • Child, Preschool
  • Concanavalin A / pharmacology
  • Cytokines / biosynthesis*
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Gene Expression
  • Genes, T-Cell Receptor beta*
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Individuality
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Stimulation, Chemical
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Tetanus Toxin / pharmacology
  • Th1 Cells / metabolism*


  • Antigens
  • Autoantigens
  • Cytokines
  • ICA1 protein, human
  • Immunoglobulin Variable Region
  • Insulin
  • Receptors, Antigen, T-Cell, alpha-beta
  • Tetanus Toxin
  • Concanavalin A