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| 1 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 2 | MHC class 11 molecules and autoimmunity显示文摘 | Nepom G T Erlich H A | 1991 | Review Immunol1991，9，： | 1 |
| 3 | Beta 57-Asp plays an essential role in the unique SDS stability of HLADQA1 * 0201/ DQB1 * 0602 alpha beta protein dimmer,the class Ⅱ MHC allele associated with protection from insulin-dependent diabetes mellitus 显示文摘 | Ettinger R A Liu A W Nepom G T | 2000 | J Immunol2000，165，： | 1 |
| 4 | MHC-DRB allellc sequences incorporate distinct intragenic trans-specific segments显示文摘 | Gaur KL Nepom GT | 1977 | Tissue Antigens1977，49，4： | 1 |
| 5 | HLA and type 1 diabetes 显示文摘 | | 1990 | Immunol Today1990，11，9： | 1 |
| 6 | HLA class Ⅱ tetramers显示文摘 | Nepom GT Bucker JH Novak EJ | 2002 | Arthritis Rheum2002，46，： | 1 |
| 7 | MHC class Ⅱ tetramers and the pursuit of antigenspecific T cells: define, deviate, delete 显示文摘 | Mallone R Nepom GT | 2004 | Clin Immunol2004，110，： | 1 |
| 8 | Prediction of susceptibility to rheumatoid arthritis by human leukozyte antigen genotyping显示文摘 | Nepom GT Nepom BS | | 0，，： | 1 |
| 9 | MHC class Ⅱ molecules and autoimmunity显示文摘 | Nepom G T Erlich H A | 1991 | Ann Rev of Immun1991，9，21： | 1 |
| 10 | MHC class II tetramers identify peptide-specific human CD4(+) T cells proliferating in response to influenza A antigen显示文摘 | Novak EJ Liu AW Nepom GT | 1999 | Journal of Clinical Investigation1999，104，： | 1 |
| 11 | Recurrence of autoimmunity in pancreas transplant patients:research update显示文摘 | Pugliese A Reijonen HK Nepom J Burke GW 3rd | | 0，，： | 1 |
| 12 | Prediction and pathogenesis in type 1 dia- betes 显示文摘 | Ziegler AG Nepom GT | 2010 | Immunity2010，32，4： | 1 |
| 13 | MHC class II tetramers identify peptide-specific human CD4+ T cells proliferating in response to influenza A antigen 显示文摘 | Novak EJ Liu AW Nepom GT Kwok WW | 1999 | J Clin Invest1999，104，12： | 1 |
| 14 | Prediction of susceptibility to rheumatoid arthritis by human leukocyte antigen genotyping显示文摘 | Nepom GT Nepom BS | 1992 | Rheum Dis Clin North Am1992，18，4： | 1 |
| 15 | CD11b^+CD28^-CD4^+ human T cells:activation requirements and association with HLADR alleles显示文摘 | Chapman A Stewart SJ Nepom GT | 1996 | J Immunol1996，157，： | 1 |
| 16 | Genetics of type 1A diabetes显示文摘 | Concannon P Rich SS Nepom GT | | 0，，： | 1 |
| 17 | MHC class II tetramers identify peptide-specific human CD4+ T cells proliferating in response to influenza a antigen显示文摘 | Liu AW Nepom GT | 1999 | J Clin Inve1999，104，： | 1 |
| 18 | Class-Ⅱ molecules and autoimmunity显示文摘 | Nepom GT Ahen J Larsson | 1996 | Immunol1996，9，： | 1 |
| 19 | Targeting T lymphoeytes for immune monitoring and intervention in autoimmune Diabetes 显示文摘 | Mallone R Nepom GT | 2005 | Am J Ther2005，12，6： | 1 |
| 20 | HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments显示文摘 | Nepom B S Haire C | 1998 | Ann Rheum Dis1998，57，4： | 1 |
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