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| Authors||G. Carcelain, P. Saint-Mezard, H. Korthals Altes, R. Tubiana, P. Grenot, C. Rabian, R.J. de Boer, D. Costagliola, C. Katlama, P. Debre, B. Autran|
|Title||Interleukin-2 therapy and thymic production of naive CD4 T cells in HIV-infected patients with severe CD4 lymhopenia|
|Faculty||Faculty of Science|
|Institute/dept.||FNWI: Institute for Biodiversity and Ecosystem Dynamics (IBED)|
|Keywords||CD4 lymphopenia; HIV; IL-2; T-cell receptor rearrangement excision circles; Thymus|
|Abstract||Objectives: IL-2 therapy increases memory and naive CD4 T cells in HIV-infected patients, but its effect on thymopoiesis is unknown. To investigate this effect, we quantified T-cell receptor rearrangement excision circles (TREC) in CD4 T cells from lymphopenic AIDS patients treated with highly active antiretroviral therapy and IL-2. Methods: CD4 cell subsets were evaluated by flow cytometry using anti-CD45RO/RA, CD62L, Ki67 and CD95 monoclonal antibodies. The proportion of recent thymic emigrant had been quantified by a real-time polymerase chain reaction assay for signal joint TREC in peripheral blood mononuclear and purified CD4 T cells. Results: At initiation of IL-2, TREC copies/l of blood were correlated with naive T cell numbers and age. Both naive and TREC numbers/l significantly increased over time in all patients, with a wide range of TREC increases. Higher percentages of CD4+CD45RO-negative cells positive for the Ki67 cell-cycle marker were found in patients with a low TREC increase, but remained stable under IL-2. TREC and naive cell recovery were correlated; they also correlated with the numbers of TREC and naive cells at the start of IL-2, and with age, suggesting a thymic origin for naive T-cell recovery. A mathematical model showing the linear recovery of naive cells and TREC under IL-2 also strongly suggested that a naive T-cell increase reflects thymic export and involves little net death and proliferation. Conclusion: Although we cannot rule out a mechanism of altered proliferation or death rate, the thymus plays an important role in the long-term recovery of naive T cells under IL-2 therapy.|
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