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A role for TNF in limiting the duration of CTL effector phase and magnitude of CD8 T cell memory.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Singh, Anju Suresh, Marulasiddappa |
| Copyright Year | 2007 |
| Abstract | It is known that TNF-alpha (TNF) exerts distinct tissue-protective or -destructive effects in the pathogenesis of T cell-dependent immunopathology, depending on the context and amount of cytokine produced. To better understand the cellular mechanisms underlying the regulation of T cells by TNF, we have analyzed the role of TNF in regulating various facets of the antigen-specific CD8 T cell response to lymphocytic choriomeningitis virus (LCMV) in mice. We show that expansion and differentiation of virus-specific effector CD8 T cells and LCMV clearance are not dependent on TNF. Instead, we demonstrate that TNF limits the duration of the effector phase of the CD8 T cell response by regulating apoptosis and not proliferation of effector cells in vivo. We further show that attenuation of effector cell apoptosis induced by TNF deficiency led to a substantial increase in the number of virus-specific memory CD8 T cells without affecting their function. The enhancement in the number of memory CD8 T cells in TNF-deficient (TNF-/-) mice was not associated with up-regulation of IL-7Ralpha or Bcl-2 in effector cells, which indicated that TNF might limit differentiation of memory cells from IL-7R(lo) effector cells. Collectively, these data are strongly suggestive of a role for TNF in down-regulating CD8 T cell responses and the establishment of CD8 T cell memory during an acute viral infection. These findings further our understanding of the regulation of CD8 T cell homeostasis and have implications in vaccine development and clinical use of anti-TNF therapies to treat T cell-dependent, inflammatory disorders. |
| Starting Page | 5 pp. |
| Ending Page | 5 pp. |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=501D7DB64CE5A02546136F24CF4885BF?doi=10.1.1.321.2635&rep=rep1&type=pdf |
| Alternate Webpage(s) | http://www.jleukbio.org/content/82/5/1201.full.pdf |
| PubMed reference number | 17704295v1 |
| Volume Number | 82 |
| Issue Number | 5 |
| Journal | Journal of leukocyte biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Cellular Phone Chronic Lymphocytic Leukemia Cytotoxic T-Lymphocytes Leukemia, B-Cell Leukemia, T-Cell Lymphocytic choriomeningitis virus Murine sarcoma viruses T-Lymphocyte Temporomandibular Joint Disorders Therapeutic procedure Transcriptional Activation Virus Diseases cytokine immunopathology specialty type I interferon receptor vaccine development |
| Content Type | Text |
| Resource Type | Article |
