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Published on: September 19, 2013
Interleukin 4 responses in acute leukaemia patients with severe chemotherapy-induced leucopenia
O Bruserud1, E Ulvestad, A Halstensen
1Section for Haematology, Gade Institute, Haukeland Hospital, University of Bergen, Norway.
Insights
T lymphocytes remain active in acute leukemia patients with chemotherapy-induced leucopenia. These cells contribute to cytokine responses, even during bacterial infections, despite fluctuating interleukin 4 (IL4) levels.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Chemotherapy for acute leukemia often causes severe leucopenia, impacting T lymphocyte function.
- Understanding T cell responses during leucopenia is crucial for managing patient immunity and infection risk.
Purpose of the Study:
- To investigate T lymphocyte activation and cytokine production in acute leukemia patients experiencing severe chemotherapy-induced leucopenia.
- To explore the role of interleukin 4 (IL4) and its soluble receptor in these patients.
Main Methods:
- Analysis of serum cytokine (IL4) and soluble receptor (sIL4R alpha) levels.
- Flow cytometry to assess T lymphocyte activation markers (CD25, CD71, HLA-DR).
- In vitro clonogenic proliferation assays of CD4+ and CD8+ T lymphocytes.
Main Results:
- Serum IL4 increased during bacterial infections, but was counteracted by increased soluble IL4 receptor alpha (sIL4R alpha).
- Activated T lymphocytes (expressing CD25, CD71, HLA-DR) were detected even in leucopenic patients.
- Proliferating T cell clones, particularly CD4+ subsets, secreted IL4.
Conclusions:
- T lymphocytes are activated and contribute to immune responses in acute leukemia patients with severe leucopenia.
- The IL4/sIL4R alpha axis plays a role in modulating T cell responses during infection in these patients.
- Activated T cells may influence patient outcomes and susceptibility to infections.
Abstract:
T lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced leucopenia were investigated using 3 different approaches: (i) analysis of serum concentrations of the T cell cytokine interleukin 4 (IL4) demonstrated that serum IL4 levels increased during complicating bacterial infections. However, this response was modulated by a concomitant increase in serum levels of the potential IL4 antagonist soluble IL4 receptor alpha chain (sIL4R alpha). (ii) Even during leucopenia a subset of T lymphocytes derived from leucopenic patients expressed the activation markers CD25 (IL2 receptor), CD71 (transferrin receptor) and HLA-DR. (iii) Subsets of circulating CD4+ and CD8+ T lymphocytes could undergo clonogenic proliferation in vitro, and a majority of these clones secreted IL4. CD4+ clones showed higher IL4 levels than CD8+ clones. Our results indicate that T lymphocytes can be activated and contribute to cytokine responses in acute leukaemia patients with severe chemotherapy-induced cytopenia.
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