The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands - PubMed (original) (raw)
The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands
Audrey L Kinter et al. J Immunol. 2008.
Abstract
The programmed death (PD)-1 molecule and its ligands (PD-L1 and PD-L2), negative regulatory members of the B7 family, play an important role in peripheral tolerance. Previous studies have demonstrated that PD-1 is up-regulated on T cells following TCR-mediated activation; however, little is known regarding PD-1 and Ag-independent, cytokine-induced T cell activation. The common gamma-chain (gamma c) cytokines IL-2, IL-7, IL-15, and IL-21, which play an important role in peripheral T cell expansion and survival, were found to up-regulate PD-1 and, with the exception of IL-21, PD-L1 on purified T cells in vitro. This effect was most prominent on memory T cells. Furthermore, these cytokines induced, indirectly, the expression of PD-L1 and PD-L2 on monocytes/macrophages in PBMC. The in vivo correlate of these observations was confirmed on PBMC isolated from HIV-infected individuals receiving IL-2 immunotherapy. Exposure of gamma c cytokine pretreated T cells to PD-1 ligand-IgG had no effect on STAT5 activation, T cell proliferation, or survival driven by gamma c cytokines. However, PD-1 ligand-IgG dramatically inhibited anti-CD3/CD28-driven proliferation and Lck activation. Furthermore, following restimulation with anti-CD3/CD28, cytokine secretion by both gamma c cytokine and anti-CD3/CD28 pretreated T cells was suppressed. These data suggest that gamma c cytokine-induced PD-1 does not interfere with cytokine-driven peripheral T cell expansion/survival, but may act to suppress certain effector functions of cytokine-stimulated cells upon TCR engagement, thereby minimizing immune-mediated damage to the host.
Similar articles
- 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.
Bennett F, Luxenberg D, Ling V, Wang IM, Marquette K, Lowe D, Khan N, Veldman G, Jacobs KA, Valge-Archer VE, Collins M, Carreno BM. Bennett F, et al. J Immunol. 2003 Jan 15;170(2):711-8. doi: 10.4049/jimmunol.170.2.711. J Immunol. 2003. PMID: 12517932 - Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production.
Brown JA, Dorfman DM, Ma FR, Sullivan EL, Munoz O, Wood CR, Greenfield EA, Freeman GJ. Brown JA, et al. J Immunol. 2003 Feb 1;170(3):1257-66. doi: 10.4049/jimmunol.170.3.1257. J Immunol. 2003. PMID: 12538684 - Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis.
Jurado JO, Alvarez IB, Pasquinelli V, Martínez GJ, Quiroga MF, Abbate E, Musella RM, Chuluyan HE, García VE. Jurado JO, et al. J Immunol. 2008 Jul 1;181(1):116-25. doi: 10.4049/jimmunol.181.1.116. J Immunol. 2008. PMID: 18566376 - Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways.
Fife BT, Bluestone JA. Fife BT, et al. Immunol Rev. 2008 Aug;224:166-82. doi: 10.1111/j.1600-065X.2008.00662.x. Immunol Rev. 2008. PMID: 18759926 Review. - PD-1 and its ligands in T-cell immunity.
Keir ME, Francisco LM, Sharpe AH. Keir ME, et al. Curr Opin Immunol. 2007 Jun;19(3):309-14. doi: 10.1016/j.coi.2007.04.012. Epub 2007 Apr 12. Curr Opin Immunol. 2007. PMID: 17433872 Review.
Cited by
- Modulation of Innate Immune Mechanisms to Enhance Leishmania Vaccine-Induced Immunity: Role of Coinhibitory Molecules.
Gannavaram S, Bhattacharya P, Ismail N, Kaul A, Singh R, Nakhasi HL. Gannavaram S, et al. Front Immunol. 2016 May 13;7:187. doi: 10.3389/fimmu.2016.00187. eCollection 2016. Front Immunol. 2016. PMID: 27242794 Free PMC article. Review. - The immunological synapse: the gateway to the HIV reservoir.
Kulpa DA, Brehm JH, Fromentin R, Cooper A, Cooper C, Ahlers J, Chomont N, Sékaly RP. Kulpa DA, et al. Immunol Rev. 2013 Jul;254(1):305-25. doi: 10.1111/imr.12080. Immunol Rev. 2013. PMID: 23772628 Free PMC article. Review. - Successful vaccination induces multifunctional memory T-cell precursors associated with early control of hepatitis C virus.
Park SH, Shin EC, Capone S, Caggiari L, De Re V, Nicosia A, Folgori A, Rehermann B. Park SH, et al. Gastroenterology. 2012 Oct;143(4):1048-60.e4. doi: 10.1053/j.gastro.2012.06.005. Epub 2012 Jun 13. Gastroenterology. 2012. PMID: 22705008 Free PMC article. - Mutation-derived Neoantigen-specific T-cell Responses in Multiple Myeloma.
Perumal D, Imai N, Laganà A, Finnigan J, Melnekoff D, Leshchenko VV, Solovyov A, Madduri D, Chari A, Cho HJ, Dudley JT, Brody JD, Jagannath S, Greenbaum B, Gnjatic S, Bhardwaj N, Parekh S. Perumal D, et al. Clin Cancer Res. 2020 Jan 15;26(2):450-464. doi: 10.1158/1078-0432.CCR-19-2309. Epub 2019 Dec 19. Clin Cancer Res. 2020. PMID: 31857430 Free PMC article. - Structure and Optimization of Checkpoint Inhibitors.
Picardo SL, Doi J, Hansen AR. Picardo SL, et al. Cancers (Basel). 2019 Dec 21;12(1):38. doi: 10.3390/cancers12010038. Cancers (Basel). 2019. PMID: 31877721 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous