Mild cold stress resulting from standard housing conditions for laboratory mice masks the severity of graft vs. host disease in mouse models of bone marrow transplantation (TRAN3P.887)
| Autor: | Nicholas Leigh, Kathleen Kokolus, Jingxin Qiu, Philip. McCarthy, Xuefang Cao, Elizabeth Repasky |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:202.26-202.26 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Clinical bone marrow transplants (BMT) yield lethal graft vs. host disease (GVHD) after transplant of un-manipulated bone marrow (BM). This differs from murine GVHD models that typically require addition of spleen or lymph node derived T cells. Recent work has shown that mice housed at mandated sub-thermoneutral ambient temperatures (22°C) are cold stressed, resulting in heat generation activated by the sympathetic nervous system. Since cold stressed mice exhibit weakened immune responses, we hypothesize that baseline GVHD is reduced compared to that seen in mice at thermoneutral temperatures (30°C). We compared GVHD in mice receiving MHC-mismatched un-manipulated BM while housed at 22 vs. 30°C at which cold stress is alleviated. In this BMT model, mice housed at 22°C show no signs of GVHD, however, we found weight loss and lethal GVHD in mice housed at 30°C. The same trend was observed with MHC-matched allogeneic BMT. As housing at 22°C activates the sympathetic nervous system, we blocked its activation by administering propranolol, a commonly prescribed β-blocker. Following BMT, mice at 22°C treated with β-blocker displayed lethal GVHD similar to untreated mice at 30°C. This suggests that T cell responses are dampened by cold stress through a β-adrenergic pathway which is circumvented by thermoneutral housing. This study provides insight into translational discrepancies of clinical and murine BMT and demonstrates lethal GVHD in a mouse model generated by un-manipulated BM. |
| Databáze: | OpenAIRE |
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