Abnormal T-cell reactivities in childhood inflammatory demyelinating disease and type 1 diabetes

Ann Neurol. 2008 Jan;63(1):98-111. doi: 10.1002/ana.21244.


Objectives: Pediatric-onset multiple sclerosis offers a unique window into early targets and mechanisms of immune dysregulation. It is unknown whether heightened T-cell reactivities documented in adult patients, to both target-organ and environmental antigens, emerge in parallel or develop as early or late events. Our objectives were to determine the presence, pattern, and specificity of abnormal T-cell reactivities to such antigens in the earliest stages of the multiple sclerosis process.

Methods: Peripheral T-cell proliferative responses to self-, dietary, and control antigens were blindly evaluated in a large cohort of well-characterized children (n = 172) with central nervous system (CNS) inflammatory demyelination (n = 63), recent-onset type 1 (insulin-dependent) diabetes mellitus (T1D; n = 41), nonautoimmune neurological conditions (n = 39), and healthy children (n = 29).

Results: Children with inflammatory demyelination, CNS injury, and T1D exhibited heightened T-cell reactivities to self-antigens, and these responses were not strictly limited to the disease target organs. Children with autoimmune disease and CNS injury also exhibited abnormal T-cell responses against multiple cow-milk proteins. Responses to specific milk epitopes distinguished T1D from inflammatory demyelination and other neurological diseases.

Interpretation: Abnormal T-cell reactivities to self- and environmental antigens manifest in the earliest clinical stages of inflammatory demyelination and T1D. The pattern of heightened T-cell reactivities implicates both shared and distinct mechanisms of immune dysregulation in the different autoimmune diseases. Abnormal T-cell responses in children with tissue injury challenge the prevailing view that CNS autoreactive cells inherently mediate the disease in early multiple sclerosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Autoantigens / immunology*
  • Autoimmunity / immunology*
  • Central Nervous System / immunology
  • Central Nervous System / physiopathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Dietary Proteins / immunology
  • Female
  • Hazardous Substances / immunology
  • Humans
  • Immune System / immunology
  • Immune System / physiopathology
  • Immune System Diseases / immunology
  • Immune System Diseases / physiopathology
  • Infant
  • Lymphocyte Activation / immunology*
  • Male
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / physiopathology
  • Self Tolerance / immunology
  • T-Lymphocytes / immunology*


  • Autoantigens
  • Dietary Proteins
  • Hazardous Substances