Interleukin (IL)-15 and IL-7 Jointly Regulate Homeostatic Proliferation of Memory Phenotype CD8+ Cells but Are Not Required for Memory Phenotype CD4+ Cells

By Joyce T. Tan, Bettina Ernst, W. Kieper, E. Leroy, J. Sprent, C. Surh. Journal of Experimental Medicine, 2002

930 citations recorded by the source corpus.

The overall size and composition of the pool of naive and memory T cells are tightly regulated by homeostatic mechanisms. Recent work has shown that homeostasis of naive T cells is controlled by two factors, self-major histocompatibility complex (MHC)/peptide ligands and a cytokine, interleukin (IL)-7. In particular, contact with these two factors is required for naive CD4+ and CD8+ cells to undergo “homeostatic” proliferation, i.e., proliferation induced as a consequence of severe T cell depletion. In contrast to naive T cells, the factors that drive memory T cells to undergo homeostatic proliferation are poorly understood. To address this issue, purified memory phenotype CD4+ and CD8+ cells from normal mice were adoptively transferred into various gene-knockout mice rendered T cell–deficient by sublethal irradiation. Three findings are reported. First, unlike naive T cells, homeostatic proliferation of memory T cells is largely MHC independent. Second, memory CD8+ cells can utilize either IL-7 or IL-15 to undergo homeostatic proliferation; however, in the absence of both IL-7 and IL-15, homeostatic proliferation fails to occur. Third, unlike memory CD8+ cells, homeostatic proliferation of memory CD4+ cells is independent of IL-7 and IL-15 (also IL-4). Thus, the homeostatic proliferation mechanisms that control memory CD8+ cells and memory CD4+ cells are quite distinct.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/ec942b927f1b8f470bc9b8c18885e1b3543e1c4c

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Citations in the corpus

• Mitochondrial Respiratory Capacity Is A Critical Regulator Of CD8+ T Cell Memory Development (2011, background): “…cytokines IL-2 and IL-15, which are critical for the development and maintenance of CD8+ Teff cells and memory T cells, respectively (Kennedy et al., 2000; Mitchell et al., 2010; Sandau et al., 2010; Schluns et al., 2002; Surh and Sprent, 2008; Tan et al., 2002; Zhang et al., 1998), influence SRC.”
• Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets (2012, neutral): “Alternately, differences in homeostatic turnover between CD4 and CD8 T cells could contribute to differences in memory accumulation, as shown by the fact that phenotypic conversion of mouse and human naive T cells to memory cells can occur because of homeostatic expansion independent of effector dif”
• Maintaining the norm: T-cell homeostasis (2002, background): “, a view that has been confirmed and also extended to CD4 + memory T cell”
• The Many Faces of IL-7: From Lymphopoiesis to Peripheral T Cell Maintenance (2005, background): “However, CD8 memory cells do require either IL-15 or IL-7 signaling, because this subset cannot be maintained in IL-15 / IL-7 / -deficient mice (52, 53).”
• CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells (2005, background): “As has been shown in other systems (60), the increased availability of homeostatic c-signaling cytokines such as IL-7, IL-15, or IL-21 could be enhancing T cell”
• Heterologous immunity provides a potent barrier to transplantation tolerance. (2003, background): “We and others have attempted to address this question experimentally and in prior studies have demonstrated that a concurrent acute infection with LCMV at the time of tolerance induction can precipitate rejection (36, 37).”