Characterization of the T-Cell Response to Coxsackievirus B4
Evidence That Effector Memory Cells Predominate in Patients With Type 1 Diabetes
Article Figures & Tables
Figures
- FIG. 1.
PAGE analysis and Coomassie staining showing the five viral CVB4 fusion proteins (VP4 to P2C lanes) and the control antigen MBP (MBP lane). M, molecular weight markers (in kDa).
- FIG. 2.
Proliferation responses against the control and viral antigens in the different study groups. Controls, healthy nondiabetic donors; FLU, influenza A virus; Long T1DM, long-standing type 1 diabetic patients; New T1DM, newly diagnosed type 1 diabetic patients. P values are indicated in the corresponding figure when <0.05. Horizontal line represents the conventional cutoff of positivity for proliferation assays (SI = 3.0).
- FIG. 3.
Correlation between T-cell proliferation responses against the VP2 coat proteins from the E2 (y-axis) and JVB (x-axis) strains of CVB4 in 19 individuals. Values are expressed as stimulation indexes (SI). A good correlation is seen between T-cell proliferative responses to E2 and JBV VP2 antigens (r2 = 0.31; P = 0.013). •, healthy control subjects; ×, newly diagnosed type 1 diabetic patients; ○, long-standing type 1 diabetic patients.
- FIG. 4.
Frequency of IFN-γ (A) and IL-4 (B) producers against the different antigens tested. ▪, healthy donors; □, newly diagnosed type 1 diabetic patients; [cjs2108], long-standing type 1 diabetic patients. The x-axis shows the antigens tested, and the y-axis shows the percentage of subjects producing the cytokine. *P = 0.004 for IL-4 production by newly diagnosed versus healthy control subjects. Flu, influenza A virus.
- FIG. 5.
IFN-γ production (pg/ml) against the different control and viral antigens in the different subject groups. Controls: healthy nondiabetic donors; Long T1DM: long-standing type 1 diabetic patients; New T1DM: newly diagnosed type 1 diabetic patients. P values are indicated in the corresponding figure when <0.05.
- FIG. 6.
Scatter plot of proliferation versus IFN-γ production among the healthy donors and newly diagnosed type 1 diabetic subjects against the CVB4 VP2 (A), VP3 (B), and P2C (C) antigens. •, healthy donors; ○, newly diagnosed type 1 diabetic patients. Responses to these CVB4 antigens are seen as IFN-γ production or proliferation, but rarely both.
Tables
- TABLE 1
Characteristics of the study groups
Control subjects Long-term type 1 diabetic subjects Newly diagnosed type 1 diabetic subject n 20 19 21 M/F (n) 13/7 13/6 12/9 Age (years) 31.2 ± 8.5 25.1 ± 8.8 29.9 ± 4 Time since diagnosis (years) N/A 5 (7 months–30 years) 0.24 (2 weeks–5 months) HLA DR 04/X* 35 42.1 33.3 HLA DR 03/X 30 21 19.1 HLA DR 04/03 5 26.3 23.8 HLA DR X/X 30 10.5 23.8 - *
* HLA DRB1 04/X includes 04/04 homozygotes; HLA DRB1 03/X includes 03/03 homozygotes. Data are means ± SD, median (range), and %, unless otherwise indicated.
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