Biphasic role of 4‐1BB in the regulation of mouse cytomegalovirus‐specific CD8+ T cells |
| |
| Authors: | Ian R. Humphreys Morgan Jones Andrea Loewendorf Emma Gostick David A. Price Chris A. Benedict Carl F. Ware Michael Croft |
| |
| Affiliation: | 1. Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA;2. Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UKThese authors have contributed equally to this work.;3. Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK |
| |
| Abstract: | The initial requirement for the emergence of CMV‐specific CD8+ T cells is poorly understood. Mice deficient in the cosignaling TNF superfamily member, 4‐1BB, surprisingly developed exaggerated early CD8+ T‐cell responses to mouse CMV (MCMV). CD8+ T cells directed against acute MCMV epitopes were enhanced, demonstrating that 4‐1BB naturally antagonizes these primary populations. Paradoxically, 4‐1BB‐deficient mice displayed reduced accumulation of memory CD8+ T cells that expand during chronic/latent infection. Importantly, the canonical TNF‐related ligand, 4‐1BBL, promoted the accumulation of these memory CD8+ T cells, whereas suppression of acute CD8+ T cells was independent of 4‐1BBL. These data highlight the dual nature of the 4‐1BB/4‐1BBL system in mediating both stimulatory and inhibitory cosignaling activities during the generation of anti‐MCMV immunity. |
| |
| Keywords: | 4‐1BB CD8+ T cells CMV Memory |
|
|
