Limits...
Impaired coronary microcirculation in type 2 diabetic patients is associated with elevated circulating regulatory T cells and reduced number of IL-21R⁺ T cells.

von Scholten BJ, Rosendahl A, Hasbak P, Bergholdt R, Kjaer A, Rossing P, Hansen TW - Cardiovasc Diabetol (2016)

Bottom Line: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression.Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR.In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetic Complications, Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark. bjos@steno.dk.

ABSTRACT

Background: Low-grade systemic inflammation is considered to participate in the progression of type 2 diabetes (T2D) and in diabetic complications.

Methods: To determine if circulating leukocytes were abnormally regulated in T2D patients, 8-color flow-cytometry (FACS) analysis was performed in a cross-sectional study of 37 T2D patients and 16 controls. Data obtained from the FACS analysis were compared to coronary flow reserve (CFR), assessed by Rb(82)-PET-imaging, to uncover inflammatory signatures associated with impaired CFR.

Results: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression. Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR. In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

Conclusions: Our demonstration that HbA1c inversely correlates to several T cell populations suggests that T cells may play disease modulating roles in T2D. Further, the novel association between impaired CFR and regulatory T cells and IL-21R(+) T cells imply an intricate balance in maintaining tissue homeostasis in vascular diabetic complications.

No MeSH data available.


Related in: MedlinePlus

Circulating lymphocyte populations in diabetic patients and healthy controls. The number of CD4 T cells (a), CD8 T cells (b), Th17 T cells (c), TfH T cells (d) and B cells (e) is shown. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4837587&req=5

Fig2: Circulating lymphocyte populations in diabetic patients and healthy controls. The number of CD4 T cells (a), CD8 T cells (b), Th17 T cells (c), TfH T cells (d) and B cells (e) is shown. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test

Mentions: The frequency of viable cells in the peripheral blood was similar in healthy and T2D patients determined as frequency of 7AAD exclusion (data not shown). On a cellular level, T2D patients was shown to have significantly (p = 0.008) lower total number of CD4+ T cells compared to healthy subjects (433 ± 24 and 579 ± 58 CD4+ T cells/µl blood respectively) (Fig. 2a). In contrast, no difference between the T2D patients and healthy subjects was discovered on CD8 T cell level (Fig. 2b). On a CD4 subset level, significant reduction of Th17 cells and a significant increase of TfH cells were observed (Fig. 2c, d). No difference between the T2D patients and healthy subjects was discovered on B cells level (Fig 2e). When adjusting for age, sex, body mass index and smoking the statistical difference between healthy and T2D patients on the CD4 level and the reduction of Th17 cells remained significant (p ≤ 0.003; Table 2).Fig. 2


Impaired coronary microcirculation in type 2 diabetic patients is associated with elevated circulating regulatory T cells and reduced number of IL-21R⁺ T cells.

von Scholten BJ, Rosendahl A, Hasbak P, Bergholdt R, Kjaer A, Rossing P, Hansen TW - Cardiovasc Diabetol (2016)

Circulating lymphocyte populations in diabetic patients and healthy controls. The number of CD4 T cells (a), CD8 T cells (b), Th17 T cells (c), TfH T cells (d) and B cells (e) is shown. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837587&req=5

Fig2: Circulating lymphocyte populations in diabetic patients and healthy controls. The number of CD4 T cells (a), CD8 T cells (b), Th17 T cells (c), TfH T cells (d) and B cells (e) is shown. A total of 2 ml blood was analysed and the total number of each cell population was calculated as described in the “Methods” section. Each dot represents one individual and the horizontal line represents the mean value in each group. P values represent difference between groups assessed by t test
Mentions: The frequency of viable cells in the peripheral blood was similar in healthy and T2D patients determined as frequency of 7AAD exclusion (data not shown). On a cellular level, T2D patients was shown to have significantly (p = 0.008) lower total number of CD4+ T cells compared to healthy subjects (433 ± 24 and 579 ± 58 CD4+ T cells/µl blood respectively) (Fig. 2a). In contrast, no difference between the T2D patients and healthy subjects was discovered on CD8 T cell level (Fig. 2b). On a CD4 subset level, significant reduction of Th17 cells and a significant increase of TfH cells were observed (Fig. 2c, d). No difference between the T2D patients and healthy subjects was discovered on B cells level (Fig 2e). When adjusting for age, sex, body mass index and smoking the statistical difference between healthy and T2D patients on the CD4 level and the reduction of Th17 cells remained significant (p ≤ 0.003; Table 2).Fig. 2

Bottom Line: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression.Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR.In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

View Article: PubMed Central - PubMed

Affiliation: Department of Diabetic Complications, Steno Diabetes Center, Niels Steensens Vej 1, 2820, Gentofte, Denmark. bjos@steno.dk.

ABSTRACT

Background: Low-grade systemic inflammation is considered to participate in the progression of type 2 diabetes (T2D) and in diabetic complications.

Methods: To determine if circulating leukocytes were abnormally regulated in T2D patients, 8-color flow-cytometry (FACS) analysis was performed in a cross-sectional study of 37 T2D patients and 16 controls. Data obtained from the FACS analysis were compared to coronary flow reserve (CFR), assessed by Rb(82)-PET-imaging, to uncover inflammatory signatures associated with impaired CFR.

Results: Presence of T2D was associated with T cell attenuation characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression. Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR. In contrast, we show, for the first time in T2D, increased TLR4 expression on CD8 T cells, increased Treg cell number and Treg maturation and reduced IL-21R expression on CD8 T cells to be functionally associated with impaired CFR.

Conclusions: Our demonstration that HbA1c inversely correlates to several T cell populations suggests that T cells may play disease modulating roles in T2D. Further, the novel association between impaired CFR and regulatory T cells and IL-21R(+) T cells imply an intricate balance in maintaining tissue homeostasis in vascular diabetic complications.

No MeSH data available.


Related in: MedlinePlus