Restricted TCR V beta gene expression and enterovirus infection in type I diabetes: a pilot study.
OBJECTIVE
High frequencies of T-cell receptor (TCR) V beta 7+ T cells were detected among the lymphocytes isolated from pancreatic islets of children at the onset of Type I (insulin-dependent) diabetes mellitus. We assessed whether a preferential expression of certain TCR V beta gene families could also be detected among the peripheral blood mononuclear cells from diabetic patients.


METHODS
T-cell receptor repertoires were evaluated by using a semi-quantitative RT-PCR-based technique and confirmed by FACS analysis in peripheral blood mononuclear cells from diabetic patients before, at and after onset of the disease. These patients were also tested for exposure to enteroviruses by RT-PCR and by measuring titres of enterovirus-specific antibodies of the IgA, IgG, and IgM classes.


RESULTS
T-cell receptor V beta 7 gene family values were higher in recently-diagnosed diabetic patients (10.5% +/- 3.7) than in age-matched non-diabetic control subjects (5.1% +/- 1.6) (p < 0.001). In a time-course analysis of people who developed diabetes during clinical monitoring (i.e., converters), T-cell receptor V beta 7 gene expression showed values consistently above 10% (p < 0.0005). Long-standing diabetic patients showed lower percentage of V beta 7 expression compared to values measured at disease onset. In the longitudinal study of the converters, multiple acute enterovirus infections were also detected. These infections appeared to be temporally related to increased percentage of V beta 7 gene transcripts.


CONCLUSIONS
The deviation in the T-cell receptor V beta repertoire among circulating T cells from diabetic patients seems to re-emphasize the importance of enterovirus infections in accelerating the progression of Type I diabetes.
Luppi
P
P
Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.
Zanone
M M
MM
Hyoty
H
H
Rudert
W A
WA
Haluszczak
C
C
Alexander
A M
AM
Bertera
S
S
Becker
D
D
Trucco
M
M
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D004769:Enterovirus Infections / Q000150:complications* / Q000276:immunology; D005260:Female; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010865:Pilot Projects; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M