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Serial study of T lymphocytes in childhood leukemia during remission
P E Lovat1, J H Robinson, K P Windebank
1Department of Immunology, University of Newcastle upon Tyne, United Kingdom.
Insights
Children undergoing maintenance chemotherapy for acute lymphoblastic leukemia (ALL) show decreased T lymphocyte numbers, particularly CD4 helper cells. This reduction, not impaired function, likely explains their increased risk of infections.
Area of Science:
- Immunology
- Pediatric Oncology
- Cellular Biology
Background:
- Maintenance chemotherapy for childhood acute lymphoblastic leukemia (cALL) can impact immune function.
- Understanding T lymphocyte changes is crucial for managing infection risk in these patients.
Purpose of the Study:
- To investigate peripheral blood T lymphocyte numbers and function in children receiving UKALL X maintenance chemotherapy.
- To compare immune parameters between children on chemotherapy and healthy controls.
Main Methods:
- Enumeration of CD4 and CD8 T lymphocyte subsets via indirect immunofluorescence.
- Assessment of specific (HSV-1) and polyclonal (Con A, PWM) T cell activation through proliferation assays and cytokine (IL-2, IL-4) production in vitro.
Main Results:
- Significant reduction in overall T lymphocyte numbers, with a more pronounced decrease in CD4+ than CD8+ T cells.
- Slight but significant decrease in T cell proliferation responses.
- No significant differences in IL-2 and IL-4 production compared to controls.
Conclusions:
- Decreased CD4 helper T cell numbers are likely the primary cause of clinical immunodeficiency in children on cALL maintenance therapy.
- This reduction in T cells, rather than impaired function, contributes to increased susceptibility to opportunistic infections.
- Findings do not support the presence of functionally defective T lymphocytes in this patient group.
Abstract:
Peripheral blood T lymphocyte numbers and function were studied in 22 children on UKALL X maintenance chemotherapy over a 2-year period, and results were compared with 20 healthy children. CD4 and CD8 subsets were enumerated using indirect immunofluorescence, and specific (HSV-1) and polyclonal (Con A, PWM) activation was studied by proliferation and IL-2/IL-4 production in vitro. T lymphocytes were significantly decreased with a greater fall in CD4 than CD8 T lymphocyte numbers. Proliferation responses were slightly but significantly decreased whereas IL-2 and IL-4 production were not significantly different from control values. These findings suggest that decreased numbers of CD4 helper T cells may be the most important factor in clinical immunodeficiency during maintenance chemotherapy for cALL contributing to increased susceptibility to opportunistic infections and argue against the presence of T lymphocytes with defective function.