Effector Functions of Donor-Reactive CD8 Memory T Cells Are Dependent on ICOS Induced During Division in Cardiac Grafts

https://doi.org/10.1111/j.1600-6143.2008.02460.xGet rights and content
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Alloreactive T-cell memory is present in every transplant recipient and endangers graft survival. Even in the absence of known sensitizing exposures, heterologous immunity and homeostatic T-cell proliferation generate ’endogenous’ memory T cells with donorreactivity. We have recently shown that endogenous donor-reactive CD8 memory T cells infiltrate murine cardiac allografts within hours of reperfusion and amplify early posttransplant inflammation by producing IFN-γ . Here, we have tested the role of ICOS costimulation in eliciting effector function from these memory T cells. ICOS is not expressed on the cell surface of circulating CD8 memory T cells but is rapidly upregulated during cell division within the allograft parenchyma. Donor-reactive CD8 memory T-cell infiltration, proliferation and ICOS expression are regulated by donor class I MHC molecule expression. ICOS blockade significantly reduced IFN-γ production and other proinflammatory functions of the activated CD8 memory T cells. Our data demonstrate that this induction of ICOS expression within peripheral tissues is an important feature of CD8 memory T-cell activation and identify ICOS as a specific target for neutralizing proinflammatory functions of endogenous CD8 memory T cells.

Keywords

Costimulation
effector mechanisms
memory CD8+ T cells
proliferation
trafficking

Abbreviations

B7RP-1
B7-related protein 1 (ICOS-L, LICOS, B7h, GL50, B7-H2, CD275)
CTLA4-Ig
cytotoxic T lymphocyte antigen 4 immunoglobulin
ICOS
inducible costimulatory molecule (CD278)
mAb
monoclonal antibody
TCR
T-cell receptor
Tg
transgenic

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