DOMINANT TCR ALPHA-CHAIN CLONOTYPES AND INTERFERON-GAMMA ARE EXPRESSED IN THE PANCREAS OF PATIENTS WITH RECENT-ONSET INSULIN-DEPENDENT DIABETES-MELLITUS
K. Yamagata et al., DOMINANT TCR ALPHA-CHAIN CLONOTYPES AND INTERFERON-GAMMA ARE EXPRESSED IN THE PANCREAS OF PATIENTS WITH RECENT-ONSET INSULIN-DEPENDENT DIABETES-MELLITUS, Diabetes research and clinical practice, 34(1), 1996, pp. 37-46
In order to clarify the nature of T lymphocytes infiltrating the pancr
eatic islets of patients with insulin-dependent diabetes mellitus (IDD
M), we analysed T cell receptor (TCR) gene transcripts expressed in pa
ncreatic biopsy specimens of patients with recent-onset IDDM. We also
investigated the expression of cytokines (interferon-gamma: IFN-gamma;
tumour necrosis factor-alpha: TNF-alpha; interleukin-4: IL-4; interle
ukin-6: IL-6) in the same specimens. The TCR V beta repertoire was not
restricted either in the pancreas or the peripheral lymphocytes of ID
DM patients. In contrast, the TCR V alpha repertoire was restricted in
the pancreas, but not in the peripheral blood lymphocytes, of IDDM pa
tients. The sequence analysis of the complementarity-determining regio
n 3 (CDR3) of the TCR alpha revealed the presence of dominant clonalit
y in alpha chains of T cells in the patients. IFN-gamma mRNA was highl
y expressed in the pancreas of IDDM patients, while IL-4 mRNA was defi
cient. A lower level of expression of IL-6 mRNA was detected in the ID
DM pancreas than in the control tissue. These results indicate that T
cells bearing a distinct TCR alpha chain are selectively retained and
activated within the pancreas of recent-onset IDDM.