scholarly journals CD4+T Cell–Dependent Reduction in Hepatitis C Virus–Specific Humoral Immune Responses after HIV Infection

2007 ◽  
Vol 195 (6) ◽  
pp. 857-863 ◽  
Author(s):  
Dale M. Netski ◽  
Tim Mosbruger ◽  
Jacquie Astemborski ◽  
Shruti H. Mehta ◽  
David L. Thomas ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Immune Responses ◽  
Hiv Infection ◽  
Cd4 T Cell ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Epistatic Effects of Immunoglobulin GM and KM Allotypes on Outcome of Infection with Hepatitis C Virus

2004 ◽  
Vol 78 (9) ◽  
pp. 4561-4565 ◽  
Author(s):  
Janardan P. Pandey ◽  
Jacquie Astemborski ◽  
David L. Thomas
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Hcv Infection ◽  
Fcγ Receptors ◽  
Epistatic Interactions ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Similar Association ◽  
Gm And Km Allotypes

ABSTRACT Immunoglobulin GM and KM allotypes—genetic markers of γ and κ chains, respectively—are associated with immune responsiveness to several infectious pathogens and with survival in certain viral epidemics. We hypothesized that GM and KM allotypes affect the outcome of hepatitis C virus (HCV) infection. To test this hypothesis, we serologically allotyped 100 persons with well-documented clearance of HCV infection and 198 matched persistently infected persons. None of the GM or KM phenotypes by itself was associated with the clearance or persistence of HCV infection. Particular combinations of these phenotypes, however, were significantly associated with the outcome of HCV infection. Subjects with GM 1,17 5,13 and KM 1,3 phenotypes were over three times (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.44 to 8.87) as likely to clear the infection as the subjects who lacked these phenotypes. This GM phenotype had a similar association with clearance in the absence of KM 3 (OR, 2.75; 95% CI, 1.21 to 6.23). The presence of GM 1,3,17 23 5,13 phenotype (in the absence of KM 3) was associated with persistence (OR, 0.21; 95% CI, 0.06 to 0.77), while its absence (in the presence of KM 1,3) was associated with the clearance of infection (OR, 2.03; 95% CI, 1.16 to 3.54). These results show epistatic interactions of genes on chromosomes 14 (GM) and 2 (KM) in influencing the outcome of an HCV infection. Further investigations involving candidate genes (GM, KM, HLA, and Fcγ receptors) and cellular and humoral immune responses to HCV epitopes are needed to understand the mechanisms underlying these associations.

A Novel Cytotoxic Mechanism by Leukemia-Specific Antibody in Immunotherapy with Leukemia Cell-Derived Heat Shock Protein 70.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2302-2302
Author(s):  
Kazuya Sato ◽  
Junko Jimbo ◽  
Takaaki Hosoki ◽  
Motohiro Shindo ◽  
Katsuya Ikuta ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Leukemia Cell ◽  
Cd4 T Cell ◽  
Leukemia Cells ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Leukemia ◽  
Mice Liver ◽  
Igg Level

Abstract Introduction: Tumor-derived heat shock proteins (HSPs), which bind the tumor-specific antigenic peptides, are good application for cancer vaccine. We previously reported that immunotherapy using leukemia cell-derived HSPs against leukemia cell in mice prolonged survival by leukemia-specific cellular immune responses through CD8 + cytotoxic T-cell (Sato et al. Blood, 2001; Iuchi et al. Int J Hematol, 2006). We also indicated that CD4+ as well as CD8+ T-cell is indispensable for the survival prolongation (Sato et al. Blood, 2001), suggesting that humoral immune response by CD4+ T-cell also contributes to eradicate leukemia cells. Contributions of humoral immune responses, including tumor-specific antibodies or cytotoxic activities, in anti-tumor immunity induced by tumor-derived HSP-based immunotherapy remain unclear. We therefore investigated humoral immune responses against leukemia cells in the leukemia cell-derived HSP70-immunized mouse model. Methods: Balb/c mice and syngeneic A20 B-cell leukemia cell line were used in this study. HSP70 was purified from A20 cells or healthy mice liver tissue. After subcutaneous administration of A20-derived HSP70 (A20-HSP), liver-derived HSP70 (liver-HSP; control) to the healthy mice, the sera were harvested to perform following experiments. To detect anti-A20 antibodies, mean fluorescence intensity (MFI) of A20 cells with mice sera and FITC-conjugated anti-mouse-IgG was analyzed by flowcytometry. The sera were subjected to ELISA to detect the specific IgG against A20-HSP, or A20 secreted IgG (A20-Ig) as an A20-specific antigen. To investigate a contribution of A20-HSP70 specific CD4+ T-cell, expression of intracellular Th2-cytokine IL4 in the A20-HSP70 stimulated CD4+ T-cell in the HSP70-immunizaed mice was measured by flowcytometry. Complement dependent cytotoxicity (CDC) activities were determined by trypan blue uptake of mouse target cells (A20, YAC1: lymphoma, or T27A: myeloid leukemia) after incubation with mice sera and complement. Results: MIF of A20 with the sera from A20-HSP immunized mice (A20-HSP mice) was significantly higher than that from liver-HSP immunized mice (liver-HSP mice). IgG level against A20-HSP by ELISA was significantly increased in the A20-HSP mice compared with liver-HSP mice. The reactivities of A20-HSP mice sera against A20-HSP were completely lost by dissociation of the antigenic peptide from A20-HSP after ATP-treatment. Additionally, IgG level against A20-Ig in the A20-HSP mice was significantly higher than that in the liver-HSP mice, and this reactivity was blocked by preincubation of the sera with A20-idiotype derived peptide (A20-IP), which is the A20-specific peptide. A20-HSP70-reactive IL4-producing CD4 + T-cells in the A20-HSP mice are extremely more than those in the liver-HSP mice. The sera from A20-HSP mice showed no cytotoxic activity itself but showed significantly high CDC activity with complement against A20 but not to YAC-1 or T27A in vitro. Conclusions: Immunization with leukemia cell-derived HSP70 induces the leukemia-specific antibodies against peptides binding to leukemia cell-derived HSP70, including B-cell leukemia idiotypic peptide, via activation of the leukemia-specific CD4+ T-cell. In addition, leukemia-specific antibody-mediated CDC contributes to the eradication of leukemia cells. To utilize the leukemia-specific CDC activities induced by HSP-based immunotherapy would be a novel therapeutic strategy to eradicate leukemia cells in the patients with leukemia.

Antigen targeting to splenic CD169+ macrophages induces strong humoral immune responses and CD4+ T cell activation

2012 ◽  
Vol 51 (1) ◽  
pp. 12-13
Author(s):  
Henrike Veninga ◽  
Ellen Borg ◽  
Hakan Kalay ◽  
Yvette van Kooyk ◽  
Georg Kraal ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Humoral Immune ◽  
Humoral Immune Responses
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