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Full-Text Articles in Medicine and Health Sciences

Kinase-Independent Function Of Rip1, Critical For Mature T-Cell Survival And Proliferation., John Bertin, Peter J. Gough, Jianke Zhang, John P. Dowling, Yubo Cai Sep 2016

Kinase-Independent Function Of Rip1, Critical For Mature T-Cell Survival And Proliferation., John Bertin, Peter J. Gough, Jianke Zhang, John P. Dowling, Yubo Cai

Department of Microbiology and Immunology Faculty Papers

The death receptor, Fas, triggers apoptotic death and is essential for maintaining homeostasis in the peripheral lymphoid organs. RIP1 was originally cloned when searching for Fas-binding proteins and was later shown to associate also with the signaling complex of TNFR1. Although Fas exclusively induces apoptosis, TNFR1 primarily activates the pro-survival/pro-inflammatory NF-κB pathway. Mutations in Fas lead to lymphoproliferative (lpr) diseases, and deletion of TNFR1 results in defective innate immune responses. However, the function of RIP1 in the adult lymphoid system has not been well understood, primarily owing to perinatal lethality in mice lacking the entire RIP1 protein in germ cells. …


Cmv-Specific Cd8 T Cell Differentiation And Localization: Implications For Adoptive Therapies., Corinne J Smith, Michael Quinn, Christopher M Snyder Sep 2016

Cmv-Specific Cd8 T Cell Differentiation And Localization: Implications For Adoptive Therapies., Corinne J Smith, Michael Quinn, Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8(+) T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8(+) T cell immunity. The aim of this review is to briefly summarize …


Ifn-Γ Receptor And Stat1 Signaling In B Cells Are Central To Spontaneous Germinal Center Formation And Autoimmunity., Phillip P. Domeier, Sathi Babu Chodisetti, Chetna Soni, Stephanie L. Schell, Melinda J. Elias, Eric B. Wong, Timothy K. Cooper, Daisuke Kitamura, Ziaur S.M. Rahman May 2016

Ifn-Γ Receptor And Stat1 Signaling In B Cells Are Central To Spontaneous Germinal Center Formation And Autoimmunity., Phillip P. Domeier, Sathi Babu Chodisetti, Chetna Soni, Stephanie L. Schell, Melinda J. Elias, Eric B. Wong, Timothy K. Cooper, Daisuke Kitamura, Ziaur S.M. Rahman

Department of Microbiology and Immunology Faculty Papers

Spontaneously developed germinal centers (GCs [Spt-GCs]) harbor autoreactive B cells that generate somatically mutated and class-switched pathogenic autoantibodies (auto-Abs) to promote autoimmunity. However, the mechanisms that regulate Spt-GC development are not clear. In this study, we report that B cell-intrinsic IFN-γ receptor (IFN-γR) and STAT1 signaling are required for Spt-GC and follicular T helper cell (Tfh cell) development. We further demonstrate that IFN-γR and STAT1 signaling control Spt-GC and Tfh cell formation by driving T-bet expression and IFN-γ production by B cells. Global or B cell-specific IFN-γR deficiency in autoimmune B6.Sle1b mice leads to significantly reduced Spt-GC and Tfh cell …


Yy1 Is Required For Germinal Center B Cell Development., Anupam Banerjee, Vishal Sindhava, Raja Vuyyuru, Vibha Jha, Suchita Hodewadekar, Tim Manser, Michael L Atchison May 2016

Yy1 Is Required For Germinal Center B Cell Development., Anupam Banerjee, Vishal Sindhava, Raja Vuyyuru, Vibha Jha, Suchita Hodewadekar, Tim Manser, Michael L Atchison

Department of Microbiology and Immunology Faculty Papers

YY1 has been implicated as a master regulator of germinal center B cell development as YY1 binding sites are frequently present in promoters of germinal center-expressed genes. YY1 is known to be important for other stages of B cell development including the pro-B and pre-B cells stages. To determine if YY1 plays a critical role in germinal center development, we evaluated YY1 expression during B cell development, and used a YY1 conditional knock-out approach for deletion of YY1 in germinal center B cells (CRE driven by the immunoglobulin heavy chain γ1 switch region promoter; γ1-CRE). We found that YY1 is …