CXCR4-mediated T cell apoptosis in human immunodeficiency virus infection.
Mechanisms of CXCR4-mediated T lymphocyte apoptosis in human immunodeficiency virus (HIV) infection are poorly understood. The authors used peripheral blood mononuclear cells isolated from HIV type 1-infected subjects and assessed both CD4(+) and CD8(+) T cell apoptosis in the presence and absence of CXCR4 blockade by AMD3100. Both CD4(+) and CD8(+) T cell apoptosis could be inhibited by CXCR4 blockade, mostly in acquired immunodeficiency syndrome subjects and more weakly in asymptomatic HIV-positive subjects, and depended only partially on the syncytium-inducing/non-syncytium-inducing viral envelope phenotype. Immune activation of CD8(+), but not CD4(+), T cells was CXCR4-dependent, resulting in increased T cell apoptosis. In the presence of monocyte-derived macrophages, CXCR4-mediated apoptosis targeted mostly CD8(+) T cells, with CD4(+) T cells being more weakly affected. Several immune and viral factors thus play a role in CXCR4-mediated T cell apoptosis in HIV infection: CD4/CD8 phenotype, viral envelope phenotype, T cell activation and T cell-macrophage intercellular contacts.
Decrion
Anne-Zélie
AZ
Department of Virology and Institut d'Etude et de Transfert de Genes, University of Franche-Comte School of Medicine, Hôpital Saint-Jacques, 2 place Saint-Jacques, F-25030 Besançon cedex, France.
Varin
Audrey
A
Department of Virology and Institut d'Etude et de Transfert de Genes, University of Franche-Comte School of Medicine, Hôpital Saint-Jacques, 2 place Saint-Jacques, F-25030 Besançon cedex, France.
Estavoyer
Jean-Marie
JM
Department of Infectious Diseases, University of Franche-Comte School of Medicine, Hôpital Saint-Jacques, 2 place Saint-Jacques, F-25030 Besançon cedex, France.
Herbein
Georges
G
Department of Virology and Institut d'Etude et de Transfert de Genes, University of Franche-Comte School of Medicine, Hôpital Saint-Jacques, 2 place Saint-Jacques, F-25030 Besançon cedex, France.
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D019718:Receptors, CXCR4