Interferon-gamma administration after abdominal surgery rescues antigen-specific helper T cell immune reactivity

Antigen-induced activation of T cells is determined by many factors. Among these factors are (i) the number of T-cell receptors (TCRs) triggered by TCR ligands on antigen-presenting cells (APCs), and (ii) the intrinsic cellular threshold for activation. T-cell receptor triggering is optimized by adhesion molecules that form the interaction site between T cells and APCs, i.e. the immunological synapse. In addition, signals through co-stimulatory molecules lower the intrinsic T-cell activation threshold. Immunosuppressive agents and traumatic events such as major operative procedures change physiological T-cell responses. Depressed immune functions after surgery are presumed to render patients more susceptible to pathogens. Interferon-gamma (IFNgamma) is a type II homodimeric cytokine with multiple immunostimulatory properties. Several studies have been performed to assess the effects of IFNgamma treatment in patients in need of increased immune reactivity. However, until now, the effect of IFNgamma on human antigen specific CD4(pos) T-cell reactivity after surgically-induced immunosuppression has not been reported. Therefore, a comparative trial of recombinant human (rh) IFNgamma versus placebo in patients after abdominal surgery was initiated. Antigen-specific helper T cell immune reactivity was assessed by antigen-induced cytokine production, intracellular cytokine staining and flow cytometry. A single dose of rhIFNgamma rescued down-modulation of antigen-specific CD4(pos) T-cell reactivity, concomitant with an up-regulation of TCR-ligands on antigen-presenting cells. Selected patients may benefit from the immunostimulatory properties of rhIFNgamma administration in vivo.