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. 2017 Nov 1;8:1447. doi: 10.3389/fimmu.2017.01447

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Copyright © 2017 Shissler, Lee and Webb.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Second signals provided by co-receptors influence invariant natural killer T (iNKT) cell biology. Stimulatory (+) pathways result in homeostatic survival and enhanced activation, cytokine production, expansion, and cytotoxicity. These positive signals come from CD44, CD161, OX40, 4-1BB, ICOS, CD40L, and CD28. Inhibitory (−) signaling can result in cell death and inhibition of iNKT cell activation. Receptors that have shown negative signaling effects include programmed death (PD)-1, B and T lymphocyte attenuator (BTLA), and lymphocyte activation gene (LAG-3). The impacts of co-receptors, such as T cell immunoglobulin mucin (TIM), CD155, CTLA-4, OX40, and GITR, are not settled in the literature and are indicated by a +/− symbol. Some co-receptors, such as CD40L, selectively skew the immune response.