Immunology

Costimulating Rejection

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Science  13 Jul 2001:
Vol. 293, Issue 5528, pp. 177
DOI: 10.1126/science.293.5528.177c

Signaling through the cell surface protein CD28 is important in the initial stages of T cell activation. However, other pathways of costimulation appear to be required for maintaining the activated state of effector T cells. Unlike CD28, the recently characterized protein-inducible costimulator (ICOS) is up-regulated after T cell activation in order to sustain T helper 2 (TH2)-type responses.

Özkaynak et al. studied the role of ICOS in T cell responses that lead to graft rejection. By preventing the interaction of ICOS with its ligand, either by use of an antibody directed against ICOS or by using an ICOS-immunoglobulin fusion protein, cardiac allograft survival in mice was prolonged. Different regimes of inhibition revealed that ICOS signaling, in addition to other pathways, was important in both the acute and chronic phases of graft rejection. Importantly, the transcription of several characteristic TH1 and TH2 genes within surviving grafts was strongly reduced, lending weight to the idea that ICOS may influence TH-1 as well as TH2 type immunity. — SJS

Nature Immunol. 2, 591 (2001).

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