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Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions
Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions
- Source :
- Nature immunology, 4(1), 49-54. Nature Publishing Group
- Publication Year :
- 2002
- Publisher :
- Springer Science and Business Media LLC, 2002.
-
Abstract
- It has been proposed that HIV-1, in addition to directly infecting and killing CD4+ T cells, causes T cell dysfunction and T cell loss by chronic immune activation. We analyzed the effects of chronic immune activation in mice that constitutively expressed CD70, the ligand for the tumor necrosis factor receptor family member CD27, on B cells. CD70 transgenic (CD70 Tg) mice showed a progressive conversion of naive T cells into effector-memory cells, which culminated in the depletion of naive T cells from lymph nodes and spleen. T cell changes depended on continuous CD27-CD70 interactions and T cell antigen receptor stimulation. Despite this hyperactive immune system, CD70 Tg mice died aged 6-8 months from Pneumocystis carinii infection, a hallmark of T cell immunodeficiency. Thus, persistent delivery of costimulatory signals via CD27-CD70 interactions, as may occur during chronic active viral infections, can exhaust the T cell pool and is sufficient to induce lethal immunodeficiency.
- Subjects :
- T-Lymphocytes
T cell
Immunology
HIV Infections
Mice, Transgenic
Biology
Lymphocyte Activation
Mice
Interleukin 21
Cytopathogenic Effect, Viral
Antigens, CD
medicine
Animals
Humans
Immunology and Allergy
Cytotoxic T cell
Lymphocyte Count
IL-2 receptor
Antigen-presenting cell
Mice, Knockout
Pneumonia, Pneumocystis
ZAP70
Immunologic Deficiency Syndromes
Membrane Proteins
CD28
Natural killer T cell
Tumor Necrosis Factor Receptor Superfamily, Member 7
Mice, Inbred C57BL
medicine.anatomical_structure
HIV-1
Immunologic Memory
CD27 Ligand
Subjects
Details
- ISSN :
- 15292916 and 15292908
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Nature Immunology
- Accession number :
- edsair.doi.dedup.....b250c11e8b19e7e12d6dca19de450b30
- Full Text :
- https://doi.org/10.1038/ni869