HLA-associated inverse correlation between T cell and antibody responsiveness to islet autoantigen in recent-onset insulin-dependent diabetes mellitus

Eur J Immunol. 1996 Jun;26(6):1285-9. doi: 10.1002/eji.1830260616.


Insulin-dependent diabetes mellitus (IDDM) is a T cell-dependent immune-mediated disease. Recently, a novel islet cell antigen (ICA69) recognized by autoantibodies was described. We tested T cell responsiveness to ICA69 in peripheral blood of patients with recent onset IDDM (n = 46), patients with long-standing IDDM (n = 44), non-diabetic age-matched, islet cell autoantibody- and glutamic acid decarboxylase (GAD)65 antibody-negative first-degree relatives of IDDM patients (n = 15) and rheumatoid arthritis patients (n = 22). T cell responsiveness was significantly higher in recent onset IDDM patients, compared to IDDM patients post-disease onset, non-diabetic first degree relatives and rheumatoid arthritis patients (p < 0.001). In responding IDDM patients a significant inverse correlation between T cell and autoantibody responsiveness to ICA69 was observed (p < 0.0005). Immunogenetic evaluation revealed an association of HLA-DR3 with T cell responsiveness to ICA69 (p < 0.02) and absence of ICA69-reactive autoantibodies (p < 0.04). The increased T cell reactivity to ICA69 in the absence of antibody reactivity at onset of IDMM is associated with an HLA class II immune response gene, and therefore suggestive of a genetically controlled selective activation of T helper subsets to a specific autoantigen in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • HLA Antigens / immunology*
  • Humans
  • Islets of Langerhans / immunology*
  • Lymphocyte Activation
  • T-Lymphocytes / immunology*
  • Time Factors


  • Autoantibodies
  • Autoantigens
  • HLA Antigens
  • ICA1 protein, human