Homeostatic turnover of virus-specific memory CD8 T cells occurs stochastically and is independent of CD4 T cell help

DK Choo, K Murali-Krishna, R Anita… - The Journal of …, 2010 - journals.aai.org
DK Choo, K Murali-Krishna, R Anita, R Ahmed
The Journal of Immunology, 2010journals.aai.org
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 …
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 (CD44 high) 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.
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