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


CONCLUSIONS
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.
Boutboul
François
F
Laboratoire d'Immunologie Cellulaire, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France.
Puthier
Denis
D
Appay
Victor
V
Pellé
Olivier
O
Ait-Mohand
Hocine
H
Combadière
Béhazine
B
Carcelain
Ghislaine
G
Katlama
Christine
C
Rowland-Jones
Sarah L
SL
Debré
Patrice
P
Nguyen
Catherine
C
Autran
Brigitte
B
D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008562:Membrane Glycoproteins / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology
D018106:CD28 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D020395:Receptors, Interleukin-7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C415350:interleukin-7 receptor, alpha chain; D054353:Perforin