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Systemic Treg Levels Are Associated with Functional Treg Differences and Correlate with the Immunological Risk in Lung Transplant Recipients
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A7761 - Systemic Treg Levels Are Associated with Functional Treg Differences and Correlate with the Immunological Risk in Lung Transplant Recipients
Author Block: G. Preissler1, E. Noessner2, G. Warnecke3, A. Knoefel3, R. Schramm4, R. Hatz1, A. Haverich3, N. Strobl1; 1Thoracic Surgery, Klinikum Grosshadern, Munich, Germany, 2Helmholtz Zentrum Muenchen, Munich, Germany, 3Clinic for Heart, Thoracic and Transplantation Surgery, Medizinische Hochschule Hannover, Hannover, Germany, 4Heart Surgery, Klinikum Grosshadern, Munich, Germany.
Rationale: Regulatory T cells (Treg) act as key modulating cells known to attenuate immune responses. However, it is not known, whether Treg levels show a patient-specific pattern before and after lung transplantation (LTX) that is associated with the incidence of acute rejection (AR). Further, it is unknown, whether functional differences, as measured by subsets like activated (aTreg) and resting Tregs (rTreg), exist in correlation to the Treg-frequency. To evaluate the potential role of Tregs as a preoperative marker for the immunological risk in LTX, T-cell immunomonitoring was performed in LTX recipients and correlated with the occurrence of AR.
Methods: In 106 recipients (m/f: 59/47, age: 53 ± 1y, LAS: 48 ± 2) before (day 0) and after (day 7, 14, 21, 90, 180, 270 and 365) LTX, T-cells (T-helper: CD3+/CD4+; Cytotoxic T Lymphocytes: CD3+/CD8+), Tregs (CD3+/CD4+/CD25+/FoxP3+) and their subsets (aTreg: CD45RAlow/-; rTreg: CD45RA+), were analyzed via Flow Cytometry. Based on Treg levels at day 0, a high (n=27, upper quartile, ≥ 6.26% of CD4+), intermediate (n=52, 50% percentile, 1.93%-6.24% of CD4+) and low (n=27, lower quartile, ≤ 1.92% of CD4+) Treg group were defined. Patients treated with steroids due to a biopsy proven (A≥1/ B≥1; n = 17) rejection episode were defined positive for AR. Data are given as mean ± SEM.
Results: Following quartile classification at day 0 (high: 8.6 ± 0.5% vs. intermediate: 4.1 ± 0.2% vs. low: 1.4 ± 0.1%), Treg levels remained stable over time and showed significant differences between all groups until day 180 (7.2 ± 0.8% vs. 5.2 ± 0.4% vs. 3.2 ± 0.7%), and between the high (6.1 ± 0.8%) and low (3.6 ± 0.5%) group until day 365. There was significantly reduced AR-rate in the high- compared to intermediate-Treg group (4% vs. 21%) and a trend towards a decreased AR-rate compared to the low-Treg group (19%). In the high-Treg group an increased frequency of aTregs (day 0: 93 ± 1% vs. low: 84 ± 2%) and a reduced frequency of rTregs (day 0: 7 ± 1% vs. low: 16 ± 2%) was found, which remained significantly different until day 180.
Conclusion: In LTX preoperative Treg quartile classification identifies an individual pattern with stable high, intermediate or low Treg levels over time. Recipients with low Tregs carried the highest immunological risk, which was associated with increased rTregs and reduced aTregs, while continuously high Treg levels appeared protective, showing the opposite functional Treg pattern.
Author Block: G. Preissler1, E. Noessner2, G. Warnecke3, A. Knoefel3, R. Schramm4, R. Hatz1, A. Haverich3, N. Strobl1; 1Thoracic Surgery, Klinikum Grosshadern, Munich, Germany, 2Helmholtz Zentrum Muenchen, Munich, Germany, 3Clinic for Heart, Thoracic and Transplantation Surgery, Medizinische Hochschule Hannover, Hannover, Germany, 4Heart Surgery, Klinikum Grosshadern, Munich, Germany.
Rationale: Regulatory T cells (Treg) act as key modulating cells known to attenuate immune responses. However, it is not known, whether Treg levels show a patient-specific pattern before and after lung transplantation (LTX) that is associated with the incidence of acute rejection (AR). Further, it is unknown, whether functional differences, as measured by subsets like activated (aTreg) and resting Tregs (rTreg), exist in correlation to the Treg-frequency. To evaluate the potential role of Tregs as a preoperative marker for the immunological risk in LTX, T-cell immunomonitoring was performed in LTX recipients and correlated with the occurrence of AR.
Methods: In 106 recipients (m/f: 59/47, age: 53 ± 1y, LAS: 48 ± 2) before (day 0) and after (day 7, 14, 21, 90, 180, 270 and 365) LTX, T-cells (T-helper: CD3+/CD4+; Cytotoxic T Lymphocytes: CD3+/CD8+), Tregs (CD3+/CD4+/CD25+/FoxP3+) and their subsets (aTreg: CD45RAlow/-; rTreg: CD45RA+), were analyzed via Flow Cytometry. Based on Treg levels at day 0, a high (n=27, upper quartile, ≥ 6.26% of CD4+), intermediate (n=52, 50% percentile, 1.93%-6.24% of CD4+) and low (n=27, lower quartile, ≤ 1.92% of CD4+) Treg group were defined. Patients treated with steroids due to a biopsy proven (A≥1/ B≥1; n = 17) rejection episode were defined positive for AR. Data are given as mean ± SEM.
Results: Following quartile classification at day 0 (high: 8.6 ± 0.5% vs. intermediate: 4.1 ± 0.2% vs. low: 1.4 ± 0.1%), Treg levels remained stable over time and showed significant differences between all groups until day 180 (7.2 ± 0.8% vs. 5.2 ± 0.4% vs. 3.2 ± 0.7%), and between the high (6.1 ± 0.8%) and low (3.6 ± 0.5%) group until day 365. There was significantly reduced AR-rate in the high- compared to intermediate-Treg group (4% vs. 21%) and a trend towards a decreased AR-rate compared to the low-Treg group (19%). In the high-Treg group an increased frequency of aTregs (day 0: 93 ± 1% vs. low: 84 ± 2%) and a reduced frequency of rTregs (day 0: 7 ± 1% vs. low: 16 ± 2%) was found, which remained significantly different until day 180.
Conclusion: In LTX preoperative Treg quartile classification identifies an individual pattern with stable high, intermediate or low Treg levels over time. Recipients with low Tregs carried the highest immunological risk, which was associated with increased rTregs and reduced aTregs, while continuously high Treg levels appeared protective, showing the opposite functional Treg pattern.
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