IL-4 and IL-15 promotion of virtual memory CD8+ T cells is determined by genetic background.
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.
['Tripathi|Pulak|P|', 'Morris|Suzanne C|SC|', 'Perkins|Charles|C|', 'Sholl|Allyson|A|', 'Finkelman|Fred D|FD|', 'Hildeman|David A|DA|']
D000818:Animals D055610:Antigens, CD1d D001117:Arenaviridae Infections D018414:CD8-Positive T-Lymphocytes D002478:Cells, Cultured D007111:Immunity, Cellular D007156:Immunologic Memory D019409:Interleukin-15 D015847:Interleukin-4 D008217:Lymphocytic choriomeningitis virus D051379:Mice D008807:Mice, Inbred BALB C D008810:Mice, Inbred C57BL D018345:Mice, Knockout D055611:Natural Killer T-Cells D016176:T-Lymphocyte Subsets
IL-4 Genetic background T-cell memory CD122 STAT6