FTY720 Effects on Inflammation and Liver Damage in a Rat Model of Renal Ischemia-Reperfusion Injury.

Objective: Ischemia-reperfusion injury (IRI) produces systemic inflammation with the potential for causing organ failure in tissues peripheral to the initial site of injury. We speculate that treatment strategies that dampen inflammation may be therapeutically beneficial to either the initial site of injury or peripheral organs. To test this, we evaluated the impact of FTY720-induced sequestration of circulating mature lymphocytes on renal IRI and secondary organ injury.

Tranexamic acid decreases rodent hemorrhagic shock-induced inflammation with mixed end-organ effects.

Beyond its anti-fibrinolytic mechanism, tranexamic acid has been suggested to have anti-inflammatory properties which may contribute to the survival benefit it provides to trauma patients. The objective of this study was to assess possible immunomodulatory effects of tranexamic acid as well as potential amelioration of end-organ injury in a rodent hemorrhagic shock model. Controlled hemorrhagic shock was induced in adult Sprague Dawley rats to a mean arterial pressure of 30 mmHg.

Induction of Skin Allograft Transplantation Tolerance in Mice Using Human Adipose Derived Stromal Cells.

Murine models of allograft transplantation are valuable for understanding the immunological mechanisms of allograft acceptance and rejection, the evaluation of immunosuppressive drugs and strategies, and the restoration of functional defects. Herein, we describe methods to create a skin murine allograft surgical model and how to administer adipose-derived stromal cells (ASC) with limited numbers of donor bone marrow to create stable multilineage donor cell chimerism and indefinite immunological tolerance.

Administration of FTY720 during Tourniquet-Induced Limb Ischemia Reperfusion Injury Attenuates Systemic Inflammation.

Acute ischemia-reperfusion injury (IRI) of the extremities leads to local and systemic inflammatory changes which can hinder limb function and can be life threatening. This study examined whether the administration of the T-cell sequestration agent, FTY720, following hind limb tourniquet-induced skeletal muscle IRI in a rat model would attenuate systemic inflammation and multiple end organ injury. Sprague-Dawley rats were subjected to 1 hr of ischemia via application of a rubber band tourniquet.

The aging immune system and its relationship with cancer.

The incidence of most common cancers increases with age. This occurs in association with, and is possibly caused by a decline in immune function, termed immune senescence. Although the size of the T-cell compartment is quantitatively maintained into older age, several deleterious changes (including significant changes to T-cell subsets) occur over time that significantly impair immunity.

Donor CD8 T cells and IFN-gamma are critical for sex-based differences in donor CD4 T cell engraftment and lupus-like phenotype in short-term chronic graft-versus-host disease mice.

The transfer of unfractionated DBA/2J (DBA) splenocytes into B6D2F(1) (DBA → F(1)) mice results in greater donor CD4 T cell engraftment in females at day 14 that persists long-term and mediates greater female lupus-like renal disease. Although donor CD8 T cells have no demonstrated role in lupus pathogenesis in this model, we recently observed that depletion of donor CD8 T cells prior to transfer eliminates sex-based differences in renal disease long-term. In this study, we demonstrate that greater day 14 female donor CD4 engraftment is also critically dependent on donor CD8 T cells.

Donor CD8 T cell activation is critical for greater renal disease severity in female chronic graft-vs.-host mice and is associated with increased splenic ICOS(hi) host CD4 T cells and IL-21 expression.

Lupus-like renal disease in DBA/2-into-F1 (DBA --> F1) mice is driven by donor CD4 T cells and is more severe in females. Donor CD8 T cells have no known role. As expected, we observed that females receiving unfractionated DBA splenocytes (CD8 intact --> F1) exhibited greater clinical and histological severities of renal disease at 13 weeks compared to males.