Malnutrition is associated with reductions in the number and function of peripheral T cells. It is unknown whether malnourishment results in the increased apoptosis of naïve T cells or whether peripheral naïve T cells are directed to another lymphoid organ such as the bone marrow, which has been shown to be a protective environment in other contexts. Therefore, we evaluated the number of naïve T cells in the bone marrow and lymph nodes of malnourished and control mice. We found that malnourished mice demonstrated enhanced naïve T cell residency in the bone marrow and diminished T cell migration to the lymph nodes. Adoptive transfer studies revealed that malnutrition has intrinsic effects on naïve T cells; control naïve T cells entered the lymph nodes and spleen more efficiently than malnourished T cells regardless of the malnutrition status of the recipient, while malnourished naïve T cells entered the bone marrow more efficiently and experienced half as much cell death there as compared to control T cells, regardless of recipient. Experiments with mice conditionally deficient for the glucocorticoid receptor in T cells demonstrated that T cell sensitivity to glucocorticoids is required for malnutrition-induced T cell migration to the bone marrow. Moreover, malnourished naive CD4+ T cells overexpress CXCR4 and CCR7 in the spleen and bone marrow, respectively, as compared to well-nourished T cells. However, malnourished naive CD4+ T cells lacking the glucocorticoid receptor express similar levels of both chemokine receptors as control T cells. Overall, we have determined that excess glucocorticoids secreted during malnutrition redirect naïve T cells to the bone marrow where they experience less cell death, perhaps due to differences in chemokine receptor expression, which may establish a modified migration pattern that allows for naïve T cell preservation in the bone marrow as well as partial preservation of immunosurveillance.
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Childhood skeletal lesions common in prehistory are present in living forager-farmers and predict adult markers of immune function
Porous cranial lesions (cribra cranii and cribra orbitalia) are widely used by archaeologists as skeletal markers of poor child health. However, their use has not been validated with systematic data from contemporary populations, where there has been little evidence of these lesions or their health relevance. Using 375 in vivo computed tomography scans from a cohort-representative sample of adults aged 40+ years from the Bolivian Amazon, among food-limited, high-mortality forager-farmers, we identified cribra cranii on 46 (12.3%) and cribra orbitalia on 23 (6%). Cribra orbitalia was associated with several hallmarks of compromised immune function, including fewer B cells, fewer naïve CD4+T cells, a lower CD4+/CD8+T cell ratio, and higher tuberculosis risk. However, neither lesion type predicted other physician-diagnosed respiratory diseases, other markers of cell-mediated immunity, or hemoglobin values. While cribra orbitalia shows promise as a skeletal indicator of health challenges, our findings do not support the continued practice of using these lesions to infer anemia in adults.
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- Award ID(s):
- 1945794
- PAR ID:
- 10656420
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Publisher / Repository:
- Science Advances
- Date Published:
- Journal Name:
- Science Advances
- Volume:
- 11
- Issue:
- 29
- ISSN:
- 2375-2548
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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