Decreased interleukin 7 responsiveness of T lymphocytes in patients with idiopathic CD4 lymphopenia
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Published on: October 15, 2013
Camille E Puronen1, William L Thompson, Hiromi Imamichi
1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Insights
Idiopathic CD4 lymphopenia (ICL) patients show reduced IL-7 signaling responsiveness in T cells. This diminished IL-7 signaling may contribute to the immune system
Area of Science:
- Immunology
- Cellular Biology
- Hematology
Background:
- Elevated serum interleukin-7 (IL-7) levels are characteristic of lymphopenic conditions.
- Idiopathic CD4 lymphopenia (ICL) is defined by low CD4 T-cell counts without known causes.
Purpose of the Study:
- To investigate if impaired IL-7 signaling contributes to the pathogenesis of ICL.
- To evaluate IL-7 receptor (IL-7Rα/CD127) expression and STAT-5 phosphorylation in ICL patients.
Main Methods:
- Peripheral blood mononuclear cells from ICL patients and healthy controls were analyzed.
- Expression of CD127 and phosphorylated STAT-5 was measured after IL-7 stimulation.
- Gene expression analysis of IL-7-induced T-cell cycling markers was performed.
Main Results:
- ICL patients exhibited lower CD4+CD127+ T cell percentages compared to controls.
- Reduced STAT-5 phosphorylation was observed in both CD4 and CD8 T cells of ICL patients.
- Decreased destabilization of p27(kip1), crucial for T-cell cycling, was noted in ICL patients.
Conclusions:
- Diminished IL-7 responsiveness in T cells is evident in ICL.
- Impaired IL-7 signaling may play a role in the T-cell count dysregulation seen in ICL.
Background:
Elevated serum interleukin 7 (IL-7) levels are observed in lymphopenic conditions, including idiopathic CD4 lymphopenia (ICL), which is characterized by CD4 lymphopenia in the absence of human immunodeficiency virus infection or other known immunodeficiency.
Methods:
To test whether defective IL-7 signaling could be an etiologic or contributing factor in ICL, peripheral blood mononuclear cells from patients with ICL (median CD4 T-cell count, 160 cells/microL) and healthy controls (median CD4 T-cell count, 582 cells/microL) were evaluated for expression of IL-7Rα chain (CD127) and intracellular phosphorylated STAT-5 (a marker of γc cytokine signaling) after cytokine stimulation. Gene expression was analyzed by real-time polymerase chain reaction following IL-7 stimulation.
Results:
The percentage of CD4+CD127+ T cells was lower in patients with ICL, compared with controls (P < .001). Lower levels of STAT-5 phosphorylation after IL-7 stimulation were observed in both CD4 and CD8 T cells from patients with ICL, compared with controls (P < .001 and P = .017, respectively), that inversely correlated in CD4 T cells with serum IL-7 levels (r = -0.734, P = .013). Destabilization of p27(kip1), a critical step for IL-7-induced T-cell cycling, was decreased in patients with ICL, compared with controls (P = .004), after IL-7 stimulation.
Conclusions:
These data suggest that diminished responsiveness to IL-7 in CD4 and CD8 T cells during ICL may be contributing to the dysregulation of T-cell homeostasis.
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