Modulation of interleukin-7 receptor expression characterizes differentiation of CD8 T cells specific for HIV, EBV and CMV

F. Boutboul Denis Puthier 1 V. Appay O. Pelle H. Ait-Mohand B. Combadiere G. Carcelain C. Katlama 2 S. L. Rowland-Jones P. Debré 3 C. Nguyen 1 B. Autran 3
1 TAGC - Technologies avancées pour le génôme et la clinique
2 Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière]
3 U3B - Unité de Biotechnologie, Biocatalyse et Biorégulation
Abstract : To further understand differentiation and homeostasis of CD8 T cells specific for HIV, Epstein-Barr Virus (EBV) and cytomegalovirus (CMV) during HIV infection, we investigated interleukin-7 receptor alpha (IL-7Ralpha) expression on those virus-specific T cells.\ Microarrays and cytometry analyses were performed on peripheral blood mononuclear cells (PBMC), total and tetramer-binding virus-specific CD8 T cells from 66 HIV-infected patients.\ Microarray analysis revealed reduced levels of IL-7Ralpha and increased levels of perforin with disease progression in total PBMC. This loss of IL-7Ralpha expression was observed on CD8 T cells and was inversely related to perforin expression. The relative expression of both molecules defined three new subsets: IL-7Ralpha(pos)Perforin(neg); IL-7Ralpha(loneg)Perforin(lo); and IL-7Ralpha(loneg)Perforin(hi) corresponding to naive and effector-memory CD8 differentiation, as assessed by CD45RA/CD11a. The IL-7Ralpha expression decreased along the CD8 differentiation pathway defined by CD27 and CD28. In contrast, IL-7Ralpha expression was down-modulated on all the CD8 T cells specific for HIV, EBV and CMV that were almost exclusively IL-7Ralpha(lo/neg)Perforin(lo) and was parallel with the CD27 expression. In addition, this low IL-7Ralpha expression on HIV-specific CD8 T cells was independent of virus load and T-cell activation and remained stable during the first 6 months of antiretroviral therapy despite successful control of HIV replication.\ The relative expression of IL-7Ralpha, perforin reveals new aspects of virus-specific CD8 T cell differentiation, independently of T-cell activation and virus load. This opens new perspectives for understanding homeostasis of those cells and immune-based therapeutic strategies.
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AIDS, Lippincott, Williams & Wilkins, 2005, 19 (17), pp.1981--1986
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https://hal-amu.archives-ouvertes.fr/hal-01595823
Contributeur : Lionel Spinelli <>
Soumis le : mercredi 27 septembre 2017 - 09:28:25
Dernière modification le : jeudi 5 avril 2018 - 10:36:21

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F. Boutboul, Denis Puthier, V. Appay, O. Pelle, H. Ait-Mohand, et al.. Modulation of interleukin-7 receptor expression characterizes differentiation of CD8 T cells specific for HIV, EBV and CMV. AIDS, Lippincott, Williams & Wilkins, 2005, 19 (17), pp.1981--1986. 〈hal-01595823〉

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