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Full-Text Articles in Medicine and Health Sciences
Selective Involvement Of The Checkpoint Regulator Vista In Suppression Of B-Cell, But Not T-Cell, Responsiveness By Monocytic Myeloid-Derived Suppressor Cells From Mice Infected With An Immunodeficiency-Causing Retrovirus, Kathy A. Green, Li Wang, Randolph J. Noelle, William R. Green
Selective Involvement Of The Checkpoint Regulator Vista In Suppression Of B-Cell, But Not T-Cell, Responsiveness By Monocytic Myeloid-Derived Suppressor Cells From Mice Infected With An Immunodeficiency-Causing Retrovirus, Kathy A. Green, Li Wang, Randolph J. Noelle, William R. Green
Dartmouth Scholarship
Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ~50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness.
Serum C-X-C Motif Chemokine 13 Is Elevated In Early And Established Rheumatoid Arthritis And Correlates With Rheumatoid Factor Levels, Jonathan D. Jones, B. Jonell Hamilton, Gregory J. Challener, Artur J. De Brum-Fernandes
Serum C-X-C Motif Chemokine 13 Is Elevated In Early And Established Rheumatoid Arthritis And Correlates With Rheumatoid Factor Levels, Jonathan D. Jones, B. Jonell Hamilton, Gregory J. Challener, Artur J. De Brum-Fernandes
Dartmouth Scholarship
We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity.
B Cell Response And Hemagglutinin Stalk-Reactive Antibody Production In Different Age Cohorts Following 2009 H1n1 Influenza Virus Vaccination, Mark Y. Sangster, Jane Baer, Felix W. Santiago, Theresa T. Fitzgerald, Natalia A. Ilyushina
B Cell Response And Hemagglutinin Stalk-Reactive Antibody Production In Different Age Cohorts Following 2009 H1n1 Influenza Virus Vaccination, Mark Y. Sangster, Jane Baer, Felix W. Santiago, Theresa T. Fitzgerald, Natalia A. Ilyushina
Dartmouth Scholarship
The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior ex- posure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated dif- ferences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and >70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) …
The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green
The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green
Dartmouth Scholarship
Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible …
Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood
Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood
Dartmouth Scholarship
There has been extensive research regarding T cell recognition of Epstein-Barr virus-transformed cells; however, less is known regarding the recognition of B cells immortalized by gamma-2 herpesviruses. Here we show that B cells immortalized by murine gammaherpesvirus 68 (MHV-68, γHV-68) can be controlled by either CD4 or CD8 T cells in vivo. We present evidence for the direct recognition of infected B cells by CD4 and CD8 T cells. These data will help in the development of immunotherapeutic approaches combating gamma-2 herpesvirus-related disease.
Myeloid-Derived Suppressor Cells In Murine Retrovirus-Induced Aids Inhibit T- And B-Cell Responses In Vitro That Are Used To Define The Immunodeficiency, Kathy A. Green, W. James Cook, William R. Green
Myeloid-Derived Suppressor Cells In Murine Retrovirus-Induced Aids Inhibit T- And B-Cell Responses In Vitro That Are Used To Define The Immunodeficiency, Kathy A. Green, W. James Cook, William R. Green
Dartmouth Scholarship
Myeloid-derived suppressor cells (MDSCs) have been characterized in several disease settings, especially in many tumor systems. Compared to their involvement in tumor microenvironments, however, MDSCs have been less well studied in their responses to infectious disease processes, in particular to retroviruses that induce immunodeficiency. Here, we demonstrate for the first time the development of a highly immunosuppressive MDSC population that is dependent on infection by the LP-BM5 retrovirus, which causes murine acquired immunodeficiency. These MDSCs express a cell surface marker signature (CD11b Gr-1 Ly6C ) characteristic of monocyte-type MDSCs. Such MDSCs profoundly inhibit immune responsiveness by a cell dose- and …
Distinction Of The Memory B Cell Response To Cognate Antigen Versus Bystander Inflammatory Signals, Micah J. Benson, Raul Elgueta, William Schpero, Michael Molloy, Weijun Zhang, Edward Usherwood, Randolph J. Noelle
Distinction Of The Memory B Cell Response To Cognate Antigen Versus Bystander Inflammatory Signals, Micah J. Benson, Raul Elgueta, William Schpero, Michael Molloy, Weijun Zhang, Edward Usherwood, Randolph J. Noelle
Dartmouth Scholarship
The hypothesis that bystander inflammatory signals promote memory B cell (BMEM) self- renewal and differentiation in an antigen-independent manner is critically evaluated herein. To comprehensively address this hypothesis, a detailed analysis is presented examining the response profiles of B-2 lineage B220 + IgG + BMEM toward cognate protein antigen in comparison to bystander inflammatory signals. After in vivo antigen encounter, quiescent BMEM clonally expand. Surprisingly, proliferating BMEM do not acquire germinal center (GC) B cell markers before generating daughter BMEM and differentiating into plasma cells or form structurally identifiable GCs. In striking contrast to …
Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle
Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle
Dartmouth Scholarship
Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can …
Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade
Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade
Dartmouth Scholarship
Cholera is an enteric disease caused by Vibrio cholerae. Toxin-coregulated pilus (TCP), a type 4 pilus expressed by V. cholerae, is a cholera virulence factor that is required for host colonization. The TCP polymer is composed of subunits of TcpA pilin. Antibodies directed against TcpA are protective in animal models of cholera. While natural or recombinant forms of TcpA are difficult to purify to homogeneity, it is anticipated that synthesized TcpA peptides might serve as immunogens in a subunit vaccine. We wanted to assess the potential for effects of the immune response (Ir) gene that could complicate a peptide-based …
Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green
Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green
Dartmouth Scholarship
Genetically susceptible C57BL/6 (B6) mice that are infected with the LP-BM5 isolate of murine retroviruses develop profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, terminal B-cell lymphomas, and an immunodeficiency state bearing many similarities to the pathologies seen in AIDS. Because of these similarities, this syndrome has been called murine AIDS (MAIDS). We have previously shown that CD154 (CD40 ligand)-CD40 molecular interactions are required both for the initiation and progression of MAIDS. Thus, in vivo anti-CD154 monoclonal antibody (MAb) treatment inhibited MAIDS symptoms in LP-BM5-infected wild-type mice when either a short course of anti-CD154 MAb treatment was started on the day of infection or …
Lineage-Restricted Function Of Nuclear Factor Kappab-Inducing Kinase (Nik) In Transducing Signals Via Cd40., Norman Garceau, Yoko Kosaka, Sally Masters, John Hambor, Reiko Shinkura, Tasuko Honjo, Randolph J. Noelle
Lineage-Restricted Function Of Nuclear Factor Kappab-Inducing Kinase (Nik) In Transducing Signals Via Cd40., Norman Garceau, Yoko Kosaka, Sally Masters, John Hambor, Reiko Shinkura, Tasuko Honjo, Randolph J. Noelle
Dartmouth Scholarship
CD40 signaling in B cells and dendritic cells (DCs) is critical for the development of humoral and cell-mediated immunity, respectively. Nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) has been implicated as a central transducing kinase in CD40-dependent activation. Here, we show that although NIK is essential for B cell activation, it is dispensable for activation of DCs. Such data provide compelling evidence that different intermediary kinases are used by different cellular lineages to trigger NF-kappaB activation via CD40.
Cd40-Cd40 Ligand Interactions In Experimental Allergic Encephalomyelitis And Multiple Sclerosis., Koen Gerritse, Jon D. Laman, Randolph J. Noelle, Alejandro Aruffo
Cd40-Cd40 Ligand Interactions In Experimental Allergic Encephalomyelitis And Multiple Sclerosis., Koen Gerritse, Jon D. Laman, Randolph J. Noelle, Alejandro Aruffo
Dartmouth Scholarship
We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological disease. CD40L-positive cells were co-localized with CD40-bearing cells in active lesions (perivascular infiltrates). Most of these CD40-bearing cells proved to be of the monocytic lineage (macrophages or microglial cells), and relatively few were B cells. To functionally evaluate CD40-CD40L interactions, EAE was elicited in mice by means of proteolipid-peptide immunization. Treatment with …