*Purpose: Cytomegalovirus (CMV) infection remains a significant issue in transplantation, especially in those who are undernourished. While undernutrition is associated with impaired T cell immunity in the general population, the mechanism in immunosuppressed patients remains unknown. We aimed to determine the differential effects of immunosuppressive medications on mCMV specific T cell immunity using a murine model of undernutrition.

*Methods: C57BL/6 mice inoculated with mCMV were either fasted for 48 hrs, an established surrogate for undernutrition, or fed ad libitum while receiving a once daily injection of either rapamycin (1mg/kg), tacrolimus (1mg/kg) or sham injection of phosphate buffer saline to serve as a control. Splenocytes were harvested and stimulated in vitro with mCMV viral peptides. T cell subsets, function and glucose uptake were examined by flow cytometry.

*Results: Non-immunosuppressed fasted mice had decreased mCMV specific T cell responses compared to non-immunosuppressed fed mice (Figure 1A; p = 0.0019). The immunosuppressant effect of fasting impaired mCMV specific T cell responses comparable to treatment with rapamycin and tacrolimus (Fig 1A). Non-immunosuppressed fasted mice had a decrease in CD8 T cell proliferation compared to non-immunosuppressed fed mice (Figure 1B; p = 0.041). Moreover, fasted mice treated with rapamycin had significantly lower CD8 T cell proliferation and relative frequency of CD8 central memory T cells (T_CM) than non-immunosuppressed fasted mice, which was not seen with tacrolimus (Figure 1B; p = 0.0003 and Figure 1C; p = 0.0005). Lastly, fasted mice receiving rapamycin had decreased glucose uptake compared to fasted mice receiving tacrolimus (Figure 1D; p = 0.043).

*Conclusions: Undernutrition has potent immunosuppressive effects on mCMV specific T cell immunity_. Rapamycin, but not tacrolimus, exacerbates the effects of undernutrition on T cell responses against mCMV and glucose metabolism. This gives insight into tailoring immunosuppressive medications in undernourished patients.

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