Journal article

Out-of-Sequence Signal 3 Paralyzes Primary CD4( ) T-Cell-Dependent Immunity.

Gail D Sckisel, Myriam N Bouchlaka, Arta M Monjazeb, Marka Crittenden, Brendan D Curti, Danice EC Wilkins, Kory A Alderson, Can M Sungur, Erik Ames, Annie Mirsoian, Abhinav Reddy, Warren Alexander, Athena Soulika, Bruce R Blazar, Dan L Longo, Robert H Wiltrout, William J Murphy

Immunity | Published : 2015


Primary T cell activation involves the integration of three distinct signals delivered in sequence: (1) antigen recognition, (2) costimulation, and (3) cytokine-mediated differentiation and expansion. Strong immunostimulatory events such as immunotherapy or infection induce profound cytokine release causing "bystander" T cell activation, thereby increasing the potential for autoreactivity and need for control. We show that during strong stimulation, a profound suppression of primary CD4(+) T-cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 (IL-2) therapy. This suppression targeted naive CD4(+) but not CD8(+) T ce..

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University of Melbourne Researchers