| First Author | Zhong X | Year | 2004 |
| Journal | Int Immunol | Volume | 16 |
| Issue | 8 | Pages | 1181-8 |
| PubMed ID | 15237109 | Mgi Jnum | J:91537 |
| Mgi Id | MGI:3047442 | Doi | 10.1093/intimm/dxh121 |
| Citation | Zhong X, et al. (2004) Suppression of expression and function of negative immune regulator PD-1 by certain pattern recognition and cytokine receptor signals associated with immune system danger. Int Immunol 16(8):1181-8 |
| abstractText | Stimulation of certain cytokine and pattern recognition receptors enhances adaptive immune responses, and in chronic situations, may play a role in the loss of self-tolerance. We hypothesized that in addition to upregulating positive immune receptors (i.e. co-stimulatory molecules), certain cytokine and pattern recognition signals might downregulate negative immune receptors, removing a potential barrier to lymphocyte responsiveness. The newly identified CD28 family member Programmed Death-1 (PD-1) is an inhibitory receptor involved in peripheral tolerance, as evidenced by the frank autoimmunity and autoantibody formation found in PD-1-deficient mice. Here we report that antigen-receptor induced PD-1 expression on murine B cells is markedly reduced by certain signals associated with immune system danger, including LPS, CpG oligodeoxynucleotides and several pro-inflammatory cytokines, through distinct signaling pathways. We further report for the first time that engagement of PD-1 inhibits cell cycle progression in primary B cells and that modulation of PD-1 expression by CpG or IL-4 significantly reverses such inhibition. Our data suggest a novel mechanism for enhancement of normal immune responses and disruption of normal tolerance mechanisms. |
