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Altered CD46-mediated T cell co-stimulation in haemodialysis patients
P-T Brinkkoetter1, S Marinaki, U Gottmann
1V. Medical Department (Nephrology), University Hospital Mannheim, University of Heidelberg, Germany. paul.brinkkoetter@med5.ma.uni-heidelberg.de
Clinical and Experimental Immunology
|February 26, 2005
Summary
Dialysis patients show altered T cell responses, with increased CD46 co-stimulation in hemodialysis (HD) and peritoneal dialysis (PD) patients. This suggests complement activation impacts acquired immunity in kidney disease.
Area of Science:
- Immunology
- Nephrology
- Cellular Biology
Background:
- Immune dysfunction in dialysis patients is often linked to CD28-CD80/86 signaling.
- The role of CD46-mediated co-stimulation in T cell activation in dialysis patients remains unexplored.
- Complement activation, involving C3b/C4b binding to CD46, occurs during hemodialysis (HD).
Purpose of the Study:
- To investigate alterations in CD46-mediated T cell activation in patients undergoing hemodialysis (HD), peritoneal dialysis (PD), and predialysis compared to healthy controls (HC).
- To assess T cell proliferation and interleukin-10 (IL-10) production following CD46 co-stimulation.
- To examine the association of these alterations with CD46 splice variants and IL-10 promoter gene polymorphisms.
Main Methods:
- Analysis of T cell surface markers, proliferation, and IL-10 production in CD4(+)T cells from HD, PD, predialysis patients, and HC.
- Co-stimulation assays using anti-CD46 and anti-CD28 antibodies.
- Reverse transcription (RT) and amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for CD46 splice variants and IL-10 polymorphisms.
Main Results:
- A significant increase in CD25 positivity on naive CD4(+)T cells was observed in all uremic patients compared to HC.
- HD and PD patients exhibited increased T cell proliferation and IL-10 production upon CD46 co-stimulation compared to CD28 co-stimulation.
- Predialysis patients and HC showed greater T cell responses with CD28 co-stimulation.
- No association was found between altered T cell responses and CD46 splice variants or IL-10 promoter polymorphisms.
Conclusions:
- T cells from hemodialysis patients demonstrate an enhanced response to CD46 co-stimulation.
- These findings suggest that ongoing complement activation during hemodialysis may contribute to acquired immune alterations in uremic patients.
- CD46-mediated co-stimulation represents a potentially significant pathway in dialysis-associated immune dysfunction.