CD4+ CD28null T cells are not alloreactive unless stimulated by interleukin-15
B Dedeoglu1, N H R Litjens1, M Klepper1
1Department of Internal Medicine, Section Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Summary
Proinflammatory CD4+ CD28null T cells show limited alloreactivity in end-stage renal disease patients. Interleukin-15 (IL-15) is crucial for their proliferation and cytotoxic potential.
Area of Science:
- Immunology
- Transplantation Immunology
Background:
- CD4+ CD28null T cells are expanded in end-stage renal disease (ESRD) patients.
- These cells are linked to rejection risk, but their alloreactive potential is unclear.
Purpose of the Study:
- To investigate the alloreactive potential and suppressive capacity of CD4+ CD28null T cells.
- To determine the role of cytokines like IL-15 in modulating their function.
Main Methods:
- Stimulation of CD4+ CD28null T cells with HLA-mismatched antigen-presenting cells.
- Evaluation of proliferation, degranulation, cytotoxicity, and cytokine production.
- Assessment of suppressive capacity on alloreactive CD28+ T cells.
Main Results:
- CD4+ CD28null T cells contained alloreactive cells but did not proliferate without IL-15.
- IL-15 induced proliferation (30.5%) and enhanced degranulation (5.8%) and cytokine production (IFN-γ, TNF-α) upon allogeneic stimulation.
- These cells demonstrated no significant suppressive capacity.
Conclusions:
- CD4+ CD28null T cells exhibit absent alloreactivity unless stimulated with IL-15.
- IL-15 is critical for activating the alloreactive and cytotoxic functions of these cells in ESRD patients.
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