Dietary restriction (DR) in mice led to a rapid decrease in memory CD8+ and CD4+ T cells in the spleen, lymph nodes, blood, and white adipose tissue and an accumulation of central memory and effector memory T cells in the bone marrow (BM). This cellular redistribution was triggered by elevated glucocorticoid levels in the blood relative to BM and was reversible with normal diet. DR remodeled the BM, increasing adipocytes, RBCs, CXCL12, and S1P, all of which contributed to T cell accumulation and retention. DR promoted energy conservation in T cells and enhanced T cell quality and protection against rechallenge with an infection or a tumor.
Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restriction (DR) but dramatically accumulated within the bone marrow (BM), where they adopted a state associated with energy conservation. This response was coordinated by glucocorticoids and associated with a profound remodeling of the BM compartment, which included an increase in T cell homing factors, erythropoiesis, and adipogenesis. Adipocytes, as well as CXCR4-CXCL12 and S1P-S1P1R interactions, contributed to enhanced T cell accumulation in BM during DR. Memory T cell homing to BM during DR was associated with enhanced protection against infections and tumors. Together, this work uncovers a fundamental host strategy to sustain and optimize immunological memory during nutritional challenges that involved a temporal and spatial reorganization of the memory pool within "safe haven" compartments.
Author Info: (1) Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
Author Info: (1) Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (2) Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (3) Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (4) Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (5) Cell Signaling Section, Laboratory of Immune System Biology, National Institutes of Health, Bethesda, MD 20892, USA. (6) Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. (7) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA. (8) Viral Immunity and Pathogenesis Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (9) Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA. (10) Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA. (11) Viral Immunity and Pathogenesis Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (12) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA. (13) Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. (14) Cell Signaling Section, Laboratory of Immune System Biology, National Institutes of Health, Bethesda, MD 20892, USA. (15) Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: ybelkaid@niaid.nih.gov.
