RT Journal Article
SR Electronic
T1 Program Death-1 Engagement Upon TCR Activation Has Distinct Effects on Costimulation and Cytokine-Driven Proliferation: Attenuation of ICOS, IL-4, and IL-21, But Not CD28, IL-7, and IL-15 Responses
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 711
OP 718
DO 10.4049/jimmunol.170.2.711
VO 170
IS 2
A1 Bennett, Frann
A1 Luxenberg, Deborah
A1 Ling, Vincent
A1 Wang, I-Ming
A1 Marquette, Kim
A1 Lowe, David
A1 Khan, Nighat
A1 Veldman, Geertruida
A1 Jacobs, Kenneth A.
A1 Valge-Archer, Viia E.
A1 Collins, Mary
A1 Carreno, Beatriz M.
YR 2003
UL http://www.jimmunol.org/content/170/2/711.abstract
AB The program death 1 (PD-1) receptor and its ligands, PD-1 ligand (PD-L)1 and PD-L2, define a novel regulatory pathway with potential inhibitory effects on T, B, and monocyte responses. In the present study, we show that human CD4+ T cells express PD-1, PD-L1, and PD-L2 upon activation, and Abs to the receptor can be agonists or antagonists of the pathway. Under optimal conditions of stimulation, ICOS but not CD28 costimulation can be prevented by PD-1 engagement. IL-2 levels induced by costimulation are critical in determining the outcome of the PD-1 engagement. Thus, low to marginal IL-2 levels produced upon ICOS costimulation account for the greater sensitivity of this pathway to PD-1-mediated inhibition. Interestingly, exogenous IL-2, IL-7, and IL-15 but not IL-4 and IL-21 can rescue PD-1 inhibition, suggesting that among these cytokines only those that activate STAT5 can rescue PD-1 inhibition. As STAT5 has been implicated in the maintenance of IL-2Rα expression, these results suggest that IL-7 and IL-15 restore proliferation under conditions of PD-1 engagement by enhancing high-affinity IL-2R expression and hence, IL-2 responsiveness.