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Insulin-secretory-granule specific T cell clones in human IDDM
J C Chang1, L G Linarelli, J A Laxer
1Immune Response Corporation, Carlsbad, CA 92008, USA.
Journal of Autoimmunity
|April 1, 1995
Summary
Researchers identified T cell clones reactive to specific beta-cell antigens in patients with type 1 diabetes (T1D). These findings suggest these antigens play a role in T1D pathogenesis and could help identify prediabetic individuals for immune intervention.
Area of Science:
- Immunology
- Endocrinology
- Autoimmune Diseases
Background:
- Type 1 diabetes (T1D) is an autoimmune disease targeting pancreatic beta cells.
- Identifying specific antigens and T cell responses is crucial for understanding T1D pathogenesis.
- Current understanding of T1D-associated antigens and pathogenic T cells remains incomplete.
Purpose of the Study:
- To identify pathogenic T cells involved in human T1D.
- To investigate the role of specific beta-cell antigens in T1D development.
- To explore potential biomarkers for early T1D detection and intervention.
Main Methods:
- Established T cell clones from T1D patients and controls.
- Utilized insulinoma cell lines (RIN and HIT) and their antigen fractions (ISG).
- Analyzed T cell cytokine profiles (Th1/Th2) and CDR3 sequences.
Main Results:
- Generated T cell clones specifically reactive to rat insulinoma ISG from T1D patients, but not controls.
- T cell clones from recent-onset T1D patients showed a Th1 profile, while prediabetic clones showed a Th2 profile.
- Identified at least two antigens in RIN-ISG recognized by dual-reactive T cell clones; these antigens were not detected in normal human or rat ISG.
Conclusions:
- Specific beta-cell antigens, particularly those found in insulinoma cell lines, are involved in T1D pathogenesis.
- The cytokine profile of T cell clones may indicate disease stage (Th1 for onset, Th2 for prediabetic).
- HIT-reactive T cells in T1D patients could aid in identifying prediabetic individuals for immune intervention strategies.