Cyclic adenosine monophosphate involvement in low-dose cyclophosphamide-reversed immune evasion in a mouse lymphoma model
| Autor: | Lili Feng, Xin Wang, Xiao-Qian Liu, Ai-Xia Dou |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Interleukin 2 Lymphoma B-Cell Immunology Intracellular Space chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Mice chemistry.chemical_compound Immune system Downregulation and upregulation Cyclic AMP medicine Animals Immunology and Allergy Cyclic adenosine monophosphate Lymphocyte Count RNA Messenger IL-2 receptor Cyclophosphamide Immune Evasion Mice Inbred BALB C Dose-Response Relationship Drug Effector Interleukin-2 Receptor alpha Subunit Forkhead Transcription Factors Survival Analysis Disease Models Animal Infectious Diseases Gene Expression Regulation chemistry CD4 Antigens Interleukin-2 cAMP-dependent pathway Intracellular Research Article medicine.drug |
| Zdroj: | Cellular & Molecular Immunology. 9:482-488 |
| ISSN: | 2042-0226 1672-7681 |
| Popis: | Lymphoma cells mobilize many mechanisms to evade the immune system. There is substantial evidence that CD4(+)CD25(+) regulatory T cells (Tregs) play a key role in the control of immune evasion. Tregs can transfer cyclic adenosine monophosphate (cAMP) to effector T cells, suggesting an association between Tregs' immune-evasion role and the intracellular cAMP pathway. In this study, we used A20 B-cell lymphoma mice as aggressive tumor models to investigate the mechanism of the depletion of Tregs by low-dose cyclophosphamide (CY, 20 mg/kg). The tumor-bearing mice had longer survival times and slower tumor growth rates following treatment with CY, but its effects were temporary. Along with the depletion of Tregs by low-dose CY treatment, the expression of interleukin-2 (IL-2) in T effector cells increased, and intracellular cAMP concentrations in immune cells decreased. Our study demonstrates the ability of low-dose CY to reverse Tregs-mediated immune evasion in a mouse model. The changes in intracellular cAMP concentrations correlated with the upregulation of effector T cells and the downregulation of Tregs, indicating the close association of cAMP analogs and low-dose CY in the immune therapy of B-cell lymphoma. |
| Databáze: | OpenAIRE |
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