| First Author | Overall SA | Year | 2017 |
| Journal | Eur J Immunol | Volume | 47 |
| Issue | 1 | Pages | 155-167 |
| PubMed ID | 27759162 | Mgi Jnum | J:249522 |
| Mgi Id | MGI:5923579 | Doi | 10.1002/eji.201646572 |
| Citation | Overall SA, et al. (2017) Increased endogenous antigen presentation in the periphery enhances susceptibility to inflammation-induced gastric autoimmunity in mice. Eur J Immunol 47(1):155-167 |
| abstractText | How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H+ /K+ ATPase alpha subunit (HKalpha) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKalpha peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice. However, increased presentation of endogenously derived HKalpha epitopes by dendritic cells (DCs) in the gastric lymph node of IE-H+ /K+ beta transgenic mice (IEbeta) reduces A23 T-cell tolerance to gastric antigens after inflammatory activation, with subsequent development of gastritis. While HKalpha-specific A23 T cells from immunised wild-type mice were poorly responsive to in vitro antigen specific activation, A23 T cells from immunised IEbeta transgenic mice were readily re-activated, indicating loss of T-cell anergy. These findings show that DCs of gastric lymph nodes can maintain tolerance of pathogenic T cells following inflammatory stimulation and that the density of endogenous antigen presented to self-reactive T cells is critical in the balance between tolerance and autoimmunity. |
