Homeostatic Turnover of Virus-Specific Memory CD8 T Cells Occurs Stochastically and Is Independent of CD4 T Cell Help
pmid: 20733203
Homeostatic Turnover of Virus-Specific Memory CD8 T Cells Occurs Stochastically and Is Independent of CD4 T Cell Help
Abstract Memory CD8 T cells persist by Ag-independent homeostatic proliferation. To examine the dynamics of this cell turnover, we transferred lymphocytic choriomeningitis virus specific memory CD8 T cells into naive mice and analyzed their in vivo division kinetics longitudinally in individual recipients.Using mathematical modeling, we determined that proliferation of this stably maintained memory CD8 T cell population was homogeneous and stochastic with a small fraction of cells completing division at any given time with an intermitotic interval of 50 d. This homeostatic turnover was comparable between memory CD8 T cells of different viral epitope specificities and also the total memory phenotype (CD44high) CD8 T cells. It is well established that CD4 T cell help is critical for maintenance of CD8 T cells during chronic infections, but recent studies have suggested that CD4 T cell help is also required for maintenance of memory CD8 T cells following acute infections. Hence, we assessed the role of CD4 T cells in Ag-independent maintenance of memory CD8 T cells. Consistent with previous reports, we found that memory CD8 T cells declined when transferred into MHC class II-deficient mice. However, their numbers were maintained stably when transferred into CD4 T cell-deficient mice. Interestingly, their homeostatic proliferation, ability to make recall responses, and phenotype were independent of CD4 T cell help because none of these qualities were affected when memory CD8 T cells were transferred and maintained in either MHC class II- or CD4-deficient recipients.
- University of Washington United States
- Emory University United States
- University of Mary United States
CD4-Positive T-Lymphocytes, Mice, Knockout, Mice, Inbred BALB C, Epitopes, T-Lymphocyte, Mice, Transgenic, CD8-Positive T-Lymphocytes, Lymphocytic Choriomeningitis, Mice, Inbred C57BL, Mice, Acute Disease, Chronic Disease, Animals, Homeostasis, Lymphocytic choriomeningitis virus, Female, Longitudinal Studies, Immunologic Memory, Cell Division, Cell Proliferation
CD4-Positive T-Lymphocytes, Mice, Knockout, Mice, Inbred BALB C, Epitopes, T-Lymphocyte, Mice, Transgenic, CD8-Positive T-Lymphocytes, Lymphocytic Choriomeningitis, Mice, Inbred C57BL, Mice, Acute Disease, Chronic Disease, Animals, Homeostasis, Lymphocytic choriomeningitis virus, Female, Longitudinal Studies, Immunologic Memory, Cell Division, Cell Proliferation
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