IL‐4 and IL‐15 promotion of virtual memory CD8+ T cells is determined by genetic background |
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Authors: | Pulak Tripathi Suzanne C. Morris Charles Perkins Allyson Sholl Fred D. Finkelman David A. Hildeman |
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Affiliation: | 1. Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, OH, USA;2. Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA;3. Departments of Medicine and Research, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA;4. Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA |
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Abstract: | Virtual memory (VM) CD8+ T cells are present in unimmunized mice, yet possess T‐cell receptors specific for foreign antigens. To date, VM cells have only been characterized in C57BL/6 mice. Here, we assessed the cytokine requirements for VM cells in C57BL/6 and BALB/c mice. As reported previously, VM cells in C57BL/6 mice rely mostly on IL‐15 and marginally on IL‐4. In stark contrast, VM cells in BALB/c mice rely substantially on IL‐4 and marginally on IL‐15. Further, NKT cells are the likely source of IL‐4, because CD1d‐deficient mice on a BALB/c background have significantly fewer VM cells. Notably, this NKT/IL‐4 axis contributes to appropriate effector and memory T‐cell responses to infection in BALB/c mice, but not in C57BL/6 mice. However, the effects of IL‐4 are manifest prior to, rather than during, infection. Thus, cytokine‐mediated control of the precursor population affects the development of virus‐specific CD8+ T‐cell memory. Depending upon the genetic background, different cytokines encountered before infection may influence the subsequent ability to mount primary and memory anti‐viral CD8+ T‐cell responses. |
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Keywords: | CD122 Genetic background IL‐4 STAT6 T‐cell memory |
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