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Inhibition of interleukin-2 receptor (CD25) expression induced on T cells from children with acute lymphoblastic
Insights
Children with acute lymphoblastic leukemia (ALL) show suppressed interleukin-2 (IL-2) receptor alpha-chain (CD25) expression on T cells at diagnosis. This defect in T-cell receptor signaling improves with remission, suggesting a temporary impairment in ALL patients.
Area of Science:
- Immunology
- Pediatric Oncology
- Molecular Biology
Background:
- Acute lymphoblastic leukemia (ALL) is a common childhood cancer.
- T-cell receptor (TCR)/CD3 complex signaling is crucial for T-cell activation and function.
- Interleukin-2 receptor alpha-chain (CD25) is a key marker of T-cell activation.
Purpose of the Study:
- To investigate the expression of CD25 on T cells in children with ALL at diagnosis.
- To identify potential defects in T-cell signaling pathways in pediatric ALL.
- To assess the recovery of CD25 expression after treatment.
Main Methods:
- Two-color flow-cytometric analysis of peripheral blood lymphocytes.
- Stimulation of T cells with anti-CD3 monoclonal antibody (mAb), phorbol 12-myristate 13-acetate (PMA), and ionomycin.
- Immune-staining analysis for protein kinase C translocation and cytoplasmic free calcium mobilization.
Main Results:
- CD25 expression was significantly suppressed on CD4+ and CD8+ T cells in a majority of children with ALL at onset.
- CD25 expression was restored in some cases with combined anti-CD3 mAb and PMA stimulation.
- CD25 inducibility was observed in most cases when stimulated with PMA plus ionomycin.
- CD25 expression upon anti-CD3 mAb stimulation recovered after complete remission was achieved.
Conclusions:
- Children with ALL at diagnosis exhibit an in vitro defect in T-cell receptor/CD3 complex signal transduction, leading to impaired CD25 expression.
- Despite the signaling defect, protein kinase C translocation and calcium mobilization appear normal.
- The recovery of CD25 expression post-remission suggests the defect is transient and potentially reversible.
Abstract:
Peripheral blood lymphocytes obtained from children with acute lymphoblastic leukemia (ALL) at onset were studied for the expression of interleukin-2 (IL-2) receptor alpha-chain (CD25) by two-color flow-cytometric analysis. Stimulated with anti-CD3 monoclonal antibody (mAb) alone. CD25 expression was significantly suppressed in CD4+ T cells from 27 of 48 (56.3%) cases and in CD8+ T cells from 29 of 48 (60.4%) cases. When stimulated with anti-CD3 mAb plus phorbol 12-myristate 13-acetate (PMA), CD25 expression was clearly restored in certain cases of ALL. When PMA plus ionomycin were used for stimulation of T cells. CD25 was inducible in a majority of cases. Interestingly CD25 expression upon anti-CD3 mAb stimulation was recovered after complete remission had been achieved. These observations suggest the presence in ALL children at onset of an in vitro defect in the signal transduction pathway of the T-cell-receptor/CD3 complex, resulting in inefficient CD25 expression. However, immune-staining analysis indicated that protein kinase C was normally translocated from the cytosol fraction to the cell membrane fraction. The mobilization of cytoplasmic free calcium is also normal.