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Terminally Differentiated CD8(+) Temra Cells Are Associated With the Risk for Acute Kidney Allograft Rejection
- Source :
- Transplantation, 94(1), 63-69. Lippincott Williams & Wilkins
- Publication Year :
- 2012
-
Abstract
- Background: End-stage renal disease (ESRD) is associated with T-cell dysregulation, leading to a variable degree of lymphopenia and increased T-cell differentiation. This may cause a relevant reduction in T-cell immunity, yielding a lowered risk for acute rejection (AR) of kidney allografts. Methods: Before kidney transplantation, circulating CD4 and CD8 + T-cell differentiation was established by determining the frequency of naive T cells, central memory and effector memory T cells, and the highly differentiated CD8 + Temra cells. In addition, the frequency of differentiated T cells without expression of the costimulatory molecule CD28 + was measured. Results: In 47 patients of the 185 patients included, a biopsy-proven AR occurred. Compared with healthy controls, T cells of patients with ESRD were significantly more differentiated. Patients with AR showed the least signs of T-cell dysregulation with significantly more T cells, more naive T cells, and less terminal differentiation of memory T cells compared with nonrejecting patients. After multivariate analysis, only the frequency of terminally differentiated CD8 + Temra cells (per percent, 4% decrease of risk [P=0.006]; per tertile, 34% decrease in risk [P=0.002]) and the number of human leukocyte antigen mismatches (per mismatch, 33% [P=0.005]) predicted the risk for AR. Functional analysis showed that CD8 Temra cells have a highly proinflammatory and cytotoxic profile. In vitro T-cell proliferation assays did not reveal a suppressor function of these cells. Conclusions: Advanced ESRD-related T-cell dysregulation that is associated with a relative increase of terminally differentiated CD8 + Temra cells protects against AR after kidney transplantation.
- Subjects :
- Graft Rejection
Male
Cellular differentiation
Human leukocyte antigen
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Risk Factors
medicine
Cytotoxic T cell
Humans
Transplantation, Homologous
Kidney transplantation
Proportional Hazards Models
Transplantation
Kidney
business.industry
Histocompatibility Testing
CD28
Cell Differentiation
Middle Aged
medicine.disease
Kidney Transplantation
medicine.anatomical_structure
Acute Disease
Cancer research
Kidney Failure, Chronic
Female
business
CD8
Subjects
Details
- ISSN :
- 00411337
- Volume :
- 94
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi.dedup.....0cdc9c9d4f459ff7e90620a1b2055a01