Chronic Exposure to Type-I IFN under Lymphopenic Conditions Alters CD4 T Cell Homeostasis

PLoS Pathogens

Adam W. Rupert¹  Zonghui Hu²  Marta Catalfamo³  H. Clifford Lane³  Lueng Tcheung³  Rebecca B. Hasley³  Mindy Smith³  Cecile Le Saout³  Michael C. Sneller³  Hiromi Imamichi³  Megan A. Luckey⁴  Jung-Hyun Park⁴  Scott K. Durum⁵ 

[1] AIDS Monitoring Labs. Leidos Biomedical Research, Inc, Frederick, Maryland, United States of America;Biostatistics Research Branch, DCR, NIAID, NIH, Bethesda, Maryland, United States of America;CMRS/Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States of America;Experimental Immunology Branch, CCR, NCI, NIH, Bethesda, Maryland, United States of America;Laboratory of Immunoregulation, CCR, NCI, NIH, Frederick, Maryland, United States of America

关键词: T cells;    Cytotoxic T cells;    T helper cells;    HIV infections;    Cloning;    Homeostasis;    Lymphopenia;    Memory T cells;   

DOI  :  10.1371/journal.ppat.1003976

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

HIV infection and the associated chronic immune activation alter T cell homeostasis leading to CD4 T cell depletion and CD8 T cell expansion. The mechanisms behind these outcomes are not totally defined and only partially explained by the direct cytopathic effect of the virus. In this manuscript, we addressed the impact of lymphopenia and chronic exposure to IFN-α on T cell homeostasis. In a lymphopenic murine model, this interaction led to decreased CD4 counts and CD8 T cell expansion in association with an increase in the Signal Transducer and Activator of Transcription 1 (STAT1) levels resulting in enhanced CD4 T cell responsiveness to IFN-α. Thus, in the setting of HIV infection, chronic stimulation of this pathway could be detrimental for CD4 T cell homeostasis.

【 授权许可】

CC BY