IL-7 is critical for homeostatic proliferation and survival of naïve T cells

IL-7 is critical for homeostatic proliferation and survival of naïve T cells

July 17, 2001 | Joyce T. Tan*, Eric Dudl*, Eric LeRoy*, Richard Murray*, Jonathan Sprent*, Kenneth I. Weinberg†, and Charles D. Surh*‡
IL-7 is essential for the homeostatic proliferation and survival of naive T cells. In T cell-deficient conditions, naive T cells undergo spontaneous homeostatic proliferation in response to self-MHC/peptide ligands. Using an in vitro system, the study shows that homeostatic proliferation is cytokine-dependent, with IL-4, IL-7, and IL-15 enhancing this process. Only IL-7 was critical for homeostatic proliferation, as naive T cells proliferated minimally in IL-7-deficient hosts. Additionally, IL-7 is crucial for the prolonged survival of naive T cells, as they disappeared gradually in IL-7-deficient hosts. In peripheral lymphoid tissues, the number of mature T cells is tightly regulated through survival, division, and death. The signals regulating T cell homeostasis are largely unknown but are thought to differ based on T cell activation/differentiation. Under normal conditions, the longevity of naive CD8+ T cells in a resting state depends on continuous contact with self-MHC/peptide ligands. Similarly, the survival of naive CD4+ cells is reported to require contact with self-MHC ligands, although this idea has been questioned. In contrast, most memory T cells survive independently of MHC and are associated with periodic cell division. CD8+ memory cells are largely controlled by IL-15, while the signals for memory CD4+ cells are still unknown. In lymphopenic conditions, both naive and memory T cells can undergo spontaneous homeostatic proliferation to restore T cell populations. Naive T cells require contact with self-MHC/peptide ligands for proliferation, while memory T cells proliferate rapidly and independently of MHC. IL-7 is essential for the survival and homeostatic proliferation of naive T cells. The study shows that IL-7 is crucial for maintaining the survival of naive T cells, as they fail to persist in IL-7-deficient hosts. The findings indicate that naive T cells depend on IL-7 for survival and homeostatic proliferation. The study also demonstrates that IL-7 is essential for homeostatic proliferation in vivo. In cytokine-gene knockout mice, homeostatic proliferation of OT-I CD8+ cells was greatly reduced in IL-7-deficient hosts but only slightly reduced in IL-4 or IL-15-deficient hosts. This suggests that IL-7 is crucial for homeostatic proliferation, with little contribution from IL-4 or IL-15. Exogenous IL-7 restored homeostatic proliferation in IL-7-deficient hosts, both in vivo and in vitro. Bcl-2 overexpression failed to replace the requirement for IL-7 in homeostatic proliferation, indicating that IL-7 is essential for this process. Survival of naive CD4+ and CD8+ T cells depends on IL-7. In experiments, naive T cells survived in IL-IL-7 is essential for the homeostatic proliferation and survival of naive T cells. In T cell-deficient conditions, naive T cells undergo spontaneous homeostatic proliferation in response to self-MHC/peptide ligands. Using an in vitro system, the study shows that homeostatic proliferation is cytokine-dependent, with IL-4, IL-7, and IL-15 enhancing this process. Only IL-7 was critical for homeostatic proliferation, as naive T cells proliferated minimally in IL-7-deficient hosts. Additionally, IL-7 is crucial for the prolonged survival of naive T cells, as they disappeared gradually in IL-7-deficient hosts. In peripheral lymphoid tissues, the number of mature T cells is tightly regulated through survival, division, and death. The signals regulating T cell homeostasis are largely unknown but are thought to differ based on T cell activation/differentiation. Under normal conditions, the longevity of naive CD8+ T cells in a resting state depends on continuous contact with self-MHC/peptide ligands. Similarly, the survival of naive CD4+ cells is reported to require contact with self-MHC ligands, although this idea has been questioned. In contrast, most memory T cells survive independently of MHC and are associated with periodic cell division. CD8+ memory cells are largely controlled by IL-15, while the signals for memory CD4+ cells are still unknown. In lymphopenic conditions, both naive and memory T cells can undergo spontaneous homeostatic proliferation to restore T cell populations. Naive T cells require contact with self-MHC/peptide ligands for proliferation, while memory T cells proliferate rapidly and independently of MHC. IL-7 is essential for the survival and homeostatic proliferation of naive T cells. The study shows that IL-7 is crucial for maintaining the survival of naive T cells, as they fail to persist in IL-7-deficient hosts. The findings indicate that naive T cells depend on IL-7 for survival and homeostatic proliferation. The study also demonstrates that IL-7 is essential for homeostatic proliferation in vivo. In cytokine-gene knockout mice, homeostatic proliferation of OT-I CD8+ cells was greatly reduced in IL-7-deficient hosts but only slightly reduced in IL-4 or IL-15-deficient hosts. This suggests that IL-7 is crucial for homeostatic proliferation, with little contribution from IL-4 or IL-15. Exogenous IL-7 restored homeostatic proliferation in IL-7-deficient hosts, both in vivo and in vitro. Bcl-2 overexpression failed to replace the requirement for IL-7 in homeostatic proliferation, indicating that IL-7 is essential for this process. Survival of naive CD4+ and CD8+ T cells depends on IL-7. In experiments, naive T cells survived in IL-
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[slides and audio] IL-7 is critical for homeostatic proliferation and survival of na%C3%AFve T cells