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OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Type

Journal article

Journal

AIDS

Publication Date

18/11/2005

Volume

19

Pages

1981 - 1986

Keywords

Antiretroviral Therapy, Highly Active, CD28 Antigens, CD8-Positive T-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytomegalovirus Infections, Epstein-Barr Virus Infections, Gene Expression, HIV Infections, HIV-1, Humans, Leukocytes, Mononuclear, Membrane Glycoproteins, Oligonucleotide Array Sequence Analysis, Perforin, Pore Forming Cytotoxic Proteins, Receptors, Interleukin-7, Transcription, Genetic, Tumor Necrosis Factor Receptor Superfamily, Member 7