Background: Reperfusion injury (RI) has significant local and systemic consequences. Ischaemic preconditioning (IPC) modulates RI and the innate immune response. This study examined whether IPC attenuates RI-mediated changes in lymphocyte populations and function following elective surgery.Methods: Twenty-five patients sustaining 1 h of tourniquet ischaemia during cruciate ligament reconstruction were randomized before surgery to three 5-min ischaemia cycles separated by 5 min of reperfusion, or to a control group. Systemic levels of interleukin (IL) 4 and interferon (IFN) gamma, and surface expression of CD45ro/ra, CD62L and CD95 were measured. T cells were examined systemically and in stimulated serum co-culture to determine CD4/CD8 and Th1/Th2 shifts through intracellular cytokine production.Results: CD4 CD45ro cell numbers increased after RI without IPC, whereas CD8 cells expressing CD45ro and CD95 increased with IPC. Preconditioned serum in co-culture attenuated increases in CD4 and decreases in CD8 numbers, a process prevented by inhibition of antigen activation. Following RI, systemic IL-2 levels were significantly lower after IPC, whereas co-culture with post-RI serum increased proinflammatory intracellular cytokine production.Conclusion: IPC modulated T cell responses in limb RI through reduced activation and proinflammatory cytokine production by CD4 cells, while preventing CD4/CD8 derangement. IPC prevented lymphocyte-directed immune dysfunction.