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Full-Text Articles in Medical Biochemistry

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen Sep 2012

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Susan H. Jackman

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …


Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen Sep 2012

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Henry Driscoll

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …


Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry Sep 2012

Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry

Susan H. Jackman

While pathogenic T cells have been identified for several diseases with epithelial cell damage, an autoimmune T cell-mediated response targeted against a known keratinocyte antigen has not been reported. Previously we described an autoimmune response directed to the mouse epidermal cell antigens, Skn. For our murine model, primed Skn-immune lymphocytes are adoptively transferred to recipients, which develop lesions at the site of mild skin trauma. In this study we investigated the nature of the autoimmune component of the Skn response. A time-course study demonstrated a relationship between the number of primed Sknimmune cells injected and the severity of skin lesions …


Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar Aug 2012

Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar

Wei-ping Zeng

Foxp3 is responsible for the major immunological features of Treg cells, including hypoproliferation in vitro, immune suppression of conventional T cells and resistance to Th2 cell differentiation. In addition to the Forkhead domain, the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper domains. To understand how these domains contribute to Foxp3 functions, we systematically compared the roles of these domains in determining the 3 major immunological features of Treg cells. We designed a bridge-mediated mutagenesis method to generate Foxp3 mutants with complete deletion of each of the domains. CD4 T cells expressing the Foxp3 mutant with deletion of …


Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar Sep 2011

Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar

Biochemistry and Microbiology

Foxp3 is responsible for the major immunological features of Treg cells, including hypoproliferation in vitro, immune suppression of conventional T cells and resistance to Th2 cell differentiation. In addition to the Forkhead domain, the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper domains. To understand how these domains contribute to Foxp3 functions, we systematically compared the roles of these domains in determining the 3 major immunological features of Treg cells. We designed a bridge-mediated mutagenesis method to generate Foxp3 mutants with complete deletion of each of the domains. CD4 T cells expressing the Foxp3 mutant with deletion of …


Modified Amino Acid Copolymers Suppress Myelin Basic Protein 85–99-Induced Encephalomyelitis In Humanized Mice Through Different Effects On T Cells, Zsolt Illés, Joel N.H. Stern, Jay Reddy, Hanspeter Waldner, Marcin P. Mycko, Celia F. Brosnan, Stephan Ellmerich, Daniel M. Altmann, Laura Santambrogio, Jack L. Strominger, Vijay K. Kuchroo Aug 2004

Modified Amino Acid Copolymers Suppress Myelin Basic Protein 85–99-Induced Encephalomyelitis In Humanized Mice Through Different Effects On T Cells, Zsolt Illés, Joel N.H. Stern, Jay Reddy, Hanspeter Waldner, Marcin P. Mycko, Celia F. Brosnan, Stephan Ellmerich, Daniel M. Altmann, Laura Santambrogio, Jack L. Strominger, Vijay K. Kuchroo

Jay Reddy Publications

A humanized mouse bearing the HLA-DR2 (DRA/DRB1*1501) pro- tein associated with multiple sclerosis (MS) and the myelin basic protein (MBP) 85–99-specific HLA-DR2-restricted T cell receptor from an MS patient has been used to examine the effectiveness of modified amino acid copolymers poly(F,Y,A,K)n and poly- (V,W,A,K)n in therapy of MBP 85–99-induced experimental auto-immune encephalomyelitis (EAE) in comparison to Copolymer 1 [Copaxone, poly(Y,E,A,K)n]. The copolymers were designed to optimize binding to HLA-DR2. Vaccination, prevention, and treatment of MBP-induced EAE in the humanized mice with copolymers FYAK and VWAK ameliorated EAE more effectively than Copolymer 1, reduced the number of pathological lesions, and …


Amelioration Of Proteolipid Protein 139–151-Induced Encephalomyelitis In Sjl Mice By Modified Amino Acid Copolymers And Their Mechanisms, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Eric Sheu, Masha Fridkis-Hareli, Hiroyuki Nishimura, Celia F. Brosnan, Laura Santambrogio, Vijay K. Kuchroo, Jack L. Strominger Jan 2004

Amelioration Of Proteolipid Protein 139–151-Induced Encephalomyelitis In Sjl Mice By Modified Amino Acid Copolymers And Their Mechanisms, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Eric Sheu, Masha Fridkis-Hareli, Hiroyuki Nishimura, Celia F. Brosnan, Laura Santambrogio, Vijay K. Kuchroo, Jack L. Strominger

Jay Reddy Publications

Copolymer 1 [Cop1, glatiramer acetate, Copaxone, poly(Y,E,A,K)n] is widely used in the treatment of relapsing/remitting multiple sclerosis in which it reduces the frequency of relapses by ≈30%. In the present study, copolymers with modified amino acid compositions (based on the binding motif of myelin basic protein 85–99 to HLA-DR2) have been developed with the aim of suppressing multiple sclerosis more effectively. The enhanced efficacy of these copolymers in experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with proteolipid protein 139–151 was demonstrated by using three protocols: (i) simultaneous administration of autoantigen and copolymer (termed prevention), (ii) …


Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry Apr 2002

Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry

Biochemistry and Microbiology

While pathogenic T cells have been identified for several diseases with epithelial cell damage, an autoimmune T cell-mediated response targeted against a known keratinocyte antigen has not been reported. Previously we described an autoimmune response directed to the mouse epidermal cell antigens, Skn. For our murine model, primed Skn-immune lymphocytes are adoptively transferred to recipients, which develop lesions at the site of mild skin trauma. In this study we investigated the nature of the autoimmune component of the Skn response. A time-course study demonstrated a relationship between the number of primed Sknimmune cells injected and the severity of skin lesions …


Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen Oct 2000

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Biochemistry and Microbiology

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …