scholarly journals Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Maria S. Salvato ◽  
C. Cameron Yin ◽  
Hideo Yagita ◽  
Toshihiro Maeda ◽  
Ko Okumura ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Immune Responses ◽  
Persistent Infection ◽  
Lymphocyte Subsets ◽  
Hiv Disease ◽  
Viral Immunity ◽  
Acute Hiv ◽  
Fas Pathway ◽  
Cell Subpopulations

Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4-lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander) cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203). Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

877 ANTI-IL10-R1 MONOCLONAL ANTIBODY ENHANCES BACILLUS CALMETTE-GUERIN (BCG) INDUCED TH1 AND ANTI-BLADDER CANCER IMMUNE RESPONSES IN VITRO AND IN VIVO

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Nathan A. Bockholt ◽  
Matthew J. Knudson ◽  
Jonathan R. Henning ◽  
Peter Weady ◽  
George J. Smith ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bladder Cancer ◽  
Immune Responses ◽  
Bacillus Calmette Guerin

Role of T cell subpopulations in mice infected with Angiostrongylus cantonensis

1996 ◽  
Vol 70 (3) ◽  
pp. 211-214 ◽  
Author(s):  
J.D. Lee ◽  
J.J. Wang ◽  
J.H. Chang ◽  
L.Y. Chung ◽  
E.R. Chen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Angiostrongylus Cantonensis ◽  
T Helper ◽  
The Third ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

AbstractWhen C57BL/6 mice were infected with Angiostrongylus cantonensis, the percentage of T helper (CD4+) cells and T supressor (CD8+) cells in peripheral blood increased weekly until the third and seventh week respectively, and then gradually decreased. C57BL/6 mice were depleted of CD4+ and CD8+ T cells by in vivo injection of anti-CD4 and anti-CD8 monoclonal antibodies, respectively, and then infected with A. cantonensis. There were significantly more and less worms recovered in the mice depleted of CD4+ and CD8+ T cells respectively than in undepleted mice. Discrete subpopulations of T cells from mice exposed to A. cantonensis for 3 weeks or 7 weeks were adoptively transferred to syngeneic recipients which were then given a challenge infection. Protection was mediated by a CD4+ T cell population present in mice after 3 weeks of infection but was not demonstrable with cells taken 7 weeks after infection. When CD4+ T cells obtained from 3-week infected mice were mixed with 5% CD8+ T cells obtained from mice infected for 7 weeks, no significant transfer of resistance was observed. Thus, immune responses to A. cantonensis in mice were regulated by discrete subpopulations of T lymphocytes.

Scavenger receptors and heat-shock protein-mediated antigen cross-presentation

2004 ◽  
Vol 32 (4) ◽  
pp. 633-635 ◽  
Author(s):  
Y. Delneste
Keyword(s):  
Monoclonal Antibody ◽  
Heat Shock ◽  
Immune Responses ◽  
Scavenger Receptors ◽  
Cross Presentation ◽  
Tumour Antigens ◽  
Shock Proteins ◽  
Human Hsp70

Heat-shock proteins (HSPs) induce protective cytotoxic immune responses against tumour antigens. This property is related to their ability to bind to and to be internalized by DC (dendritic cells) before gaining access to the MHC class I processing pathway, a process called antigen cross-presentation. This process requires internalization of the antigen by DC via endocytic receptors. Owing to their particular immune properties, several studies were focused on the identification of HSP-binding elements on DC. We and others have reported that scavenger receptors are the main HSP-binding structures on human DC and have identified LOX-1 as one of these molecules. The binding of human Hsp70 to DC and the in vitro Hsp70-mediated antigen cross-presentation are inhibited by an anti-LOX-1 monoclonal antibody. In vivo, targeting LOX-1 with a tumour antigen using an anti-LOX-1 monoclonal antibody induces antitumour immunity. Thus scavenger receptors are certainly new promising targets for cancer immunotherapy.

Lymphocyte recirculation, exercise, and immune responses

1998 ◽  
Vol 76 (5) ◽  
pp. 490-496 ◽  
Author(s):  
John B Hay ◽  
William N Andrade
Keyword(s):  
Immune Responses ◽  
Cell Tracking ◽  
Lymphocyte Subsets ◽  
Blood Pool ◽  
Exercise Stress ◽  
Lymphocyte Migration ◽  
Blood Samples ◽  
Lymphocyte Recirculation ◽  
Afferent Lymph

Alterations in leukocyte concentrations in the blood are associated with exercise, stress, and other pathophysiological perturbations. The continuous migration and redistribution of cells of the recirculating lymphocyte pool between the blood and lymphatic systems can be influenced by a variety of physiological, immunological, and pathological processes. The phenotypic distribution of lymphocyte subsets is not the same in blood, afferent lymph, and efferent lymph, and cell-tracking experiments have shown that lymphocytes vary in their migratory properties. The most comprehensive physiological studies tracking these cells in vivo have been done in sheep. It has been shown that lymph-derived cells have different migratory capacities than blood-derived lymphocytes, that antigenic challenge of a single lymph node can first reduce the output of lymphocytes from the node and then markedly increase the recruitment from the blood and subsequently the output into efferent lymph. In most mammals, the blood pool of lymphocytes represents only about 1% of the total lymphocytes and only a small fraction of the recirculating lymphocyte pool. Therefore, testing the effects of exercise on lymphocyte recirculation by examining blood samples only requires considerable deduction and inference to interpret multicompartmental effects.Key words: lymphocyte migration, blood, lymph, lymph nodes.

The Anticoagulant Properties of a Modified Form of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 298-304 ◽  
Author(s):  
C A Mitchell ◽  
S M Kelemen ◽  
H H Salem
Keyword(s):  
Monoclonal Antibody ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor Xa ◽  
Protein S ◽  
Human Neutrophil Elastase ◽  
Factor X ◽  
Sds Page

SummaryProtein S (PS) is a vitamin K-dependent anticoagulant that acts as a cofactor to activated protein C (APC). To date PS has not been shown to possess anticoagulant activity in the absence of APC.In this study, we have developed monoclonal antibody to protein S and used to purify the protein to homogeneity from plasma. Affinity purified protein S (PSM), although identical to the conventionally purified protein as judged by SDS-PAGE, had significant anticoagulant activity in the absence of APC when measured in a factor Xa recalcification time. Using SDS-PAGE we have demonstrated that prothrombin cleavage by factor X awas inhibited in the presence of PSM. Kinetic analysis of the reaction revealed that PSM competitively inhibited factor X amediated cleavage of prothrombin. PS preincubated with the monoclonal antibody, acquired similar anticoagulant properties. These results suggest that the interaction of the monoclonal antibody with PS results in an alteration in the protein exposing sites that mediate the observed anticoagulant effect. Support that the protein was altered was derived from the observation that PSM was eight fold more sensitive to cleavage by thrombin and human neutrophil elastase than conventionally purified protein S.These observations suggest that PS can be modified in vitro to a protein with APC-independent anticoagulant activity and raise the possibility that a similar alteration could occur in vivo through the binding protein S to a cellular or plasma protein.

Effects of a Monoclonal Antibody to Glycoprotein IIb/IIIa (P256) and of Enzymically Derived Fragments of P256 on Human Platelets

1991 ◽  
Vol 65 (04) ◽  
pp. 432-437 ◽  
Author(s):  
A W J Stuttle ◽  
M J Powling ◽  
J M Ritter ◽  
R M Hardisty
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Platelet Aggregation ◽  
Calcium Ions ◽  
Human Platelet ◽  
Human Platelets ◽  
In Vivo Detection ◽  
Fibrinogen Binding ◽  
Specific Antagonist

SummaryThe anti-platelet monoclonal antibody P256 is currently undergoing development for in vivo detection of thrombus. We have examined the actions of P256 and two fragments on human platelet function. P256, and its divalent fragment, caused aggregation at concentrations of 10−9−3 × 10−8 M. A monovalent fragment of P256 did not cause aggregation at concentrations up to 10−7 M. P256–induced platelet aggregation was dependent upon extracellular calcium ions as assessed by quin2 fluorescence. Indomethacin partially inhibited platelet aggregation and completely inhibited intracellular calcium mobilisation. Apyrase caused partial inhibition of aggregation. Aggregation induced by the divalent fragment was dependent upon fibrinogen and was inhibited by prostacyclin. Aggregation induced by the whole antibody was only partially dependent upon fibrinogen, but was also inhibited by prostacyclin. P256 whole antibody was shown, by flow cytometry, to induce fibrinogen binding to indomethacin treated platelets. Monovalent P256 was shown to be a specific antagonist for aggregation induced by the divalent forms. In–111–labelled monovalent fragment bound to gel-filtered platelets in a saturable and displaceable manner. Monovalent P256 represents a safer form for in vivo applications

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