 |
|
New study shows antibody-interleukin complexes stimulate immune responses
February 23, 2006Selective T cell stimulation could help improve treatment of autoimmune disease and cancer
The findings could also be significant for developing new ways to help patients with autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or juvenile diabetes.
The study, which was published in the February 16 issue of the online journal Science Express, showed that these injections caused a massive selective increase in the immune system's two main types of T cells.
"Our study shows that different cytokine-antibody complexes such as IL-2/IL-2 mAb could be clinically useful to selectively boost or inhibit the immune response in vivo," said Onur Boyman, a member of the Scripps Research Department of Immunology and lead author of the study.
The type of monoclonal antibody that was injected was specific to interleukin-2 (IL-2), a naturally occurring protein and a known immunotherapy for metastatic melanoma and renal cancer. The researchers showed that the anti-IL-2 monoclonal antibody (IL-2 mAb) expands the proliferation of specific T cells in vivo by increasing the biological activity of naturally occurring IL-2 through the formation of immune complexes. When combined with recombinant IL-2, some IL-2/IL-2 mAb complexes cause more than a 100-fold proliferation in CD8+ T cells, which can target virally infected cells or tumor cells.
Interleukin-2 increases the number of a subset of CD8+ T cells (referred to as antigen-experienced or memory T cells) in circulation and is often used for tumor immunotherapy and vaccination. However, IL-2 also stimulates CD4+ T regulatory cells, which can suppress those same memory T cells. Therefore, the prevailing view was that administration of IL-2 mAb removes the IL-2-dependent CD4+ T regulatory cells, which in turn leads to an expansion of CD8+ T cells.
"In the study, however, we noticed that the enhancing effect of IL-2 mAb correlated with naturally occurring levels of IL-2," Boyman said. "We concluded that, despite its reported neutralizing effect, IL-2 mAb actually expanded the proliferation of CD8+ T cells simply by increasing the biological activity of pre-existing IL-2 through the formation of antibody-cytokine immune complexes in vivo. We next combined recombinant IL-2 with IL-2 mAb, which led to an even more dramatic expansion. This expansion effect also extended to other types of antibody-cytokine complexes, such as IL-4/IL-4 mAb and IL-7/IL-7 mAb."
Despite these findings, Boyman noted, no one yet knows why these antibody-cytokine complexes are such potent immune response boosters in vivo.
"A few studies have suggested that injecting a cytokine together with the right antibody increases the half-life of the cytokine in vivo, accompanied by a very mild immune activation," he said. "But our study suggests a different mechanism and that joining a cytokine to its specific antibody opens the way for selective and vigorous stimulation of T cell subsets. With some types of antibodies, injecting IL-2/IL-2 mAb complexes might be clinically useful for tumor immunotherapy and for expanding T cell numbers after bone marrow transplantation. On the other hand, expansion of CD4+ T regulatory cells by IL-2 combined with another type of IL-2 mAb might provide a basis for treating autoimmune disease."
Scripps Research Institute
"Our study shows that different cytokine-antibody complexes such as IL-2/IL-2 mAb could be clinically useful to selectively boost or inhibit the immune response in vivo," said Onur Boyman, a member of the Scripps Research Department of Immunology and lead author of the study.
The type of monoclonal antibody that was injected was specific to interleukin-2 (IL-2), a naturally occurring protein and a known immunotherapy for metastatic melanoma and renal cancer. The researchers showed that the anti-IL-2 monoclonal antibody (IL-2 mAb) expands the proliferation of specific T cells in vivo by increasing the biological activity of naturally occurring IL-2 through the formation of immune complexes. When combined with recombinant IL-2, some IL-2/IL-2 mAb complexes cause more than a 100-fold proliferation in CD8+ T cells, which can target virally infected cells or tumor cells.
Interleukin-2 increases the number of a subset of CD8+ T cells (referred to as antigen-experienced or memory T cells) in circulation and is often used for tumor immunotherapy and vaccination. However, IL-2 also stimulates CD4+ T regulatory cells, which can suppress those same memory T cells. Therefore, the prevailing view was that administration of IL-2 mAb removes the IL-2-dependent CD4+ T regulatory cells, which in turn leads to an expansion of CD8+ T cells.
"In the study, however, we noticed that the enhancing effect of IL-2 mAb correlated with naturally occurring levels of IL-2," Boyman said. "We concluded that, despite its reported neutralizing effect, IL-2 mAb actually expanded the proliferation of CD8+ T cells simply by increasing the biological activity of pre-existing IL-2 through the formation of antibody-cytokine immune complexes in vivo. We next combined recombinant IL-2 with IL-2 mAb, which led to an even more dramatic expansion. This expansion effect also extended to other types of antibody-cytokine complexes, such as IL-4/IL-4 mAb and IL-7/IL-7 mAb."
Despite these findings, Boyman noted, no one yet knows why these antibody-cytokine complexes are such potent immune response boosters in vivo.
"A few studies have suggested that injecting a cytokine together with the right antibody increases the half-life of the cytokine in vivo, accompanied by a very mild immune activation," he said. "But our study suggests a different mechanism and that joining a cytokine to its specific antibody opens the way for selective and vigorous stimulation of T cell subsets. With some types of antibodies, injecting IL-2/IL-2 mAb complexes might be clinically useful for tumor immunotherapy and for expanding T cell numbers after bone marrow transplantation. On the other hand, expansion of CD4+ T regulatory cells by IL-2 combined with another type of IL-2 mAb might provide a basis for treating autoimmune disease."
Scripps Research Institute
Immune Response Current Events and Immune Response News RSSCommon pain relief medication may encourage cancer growth
Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells.
New culprit for viral infections among elderly -- an overactive immune response
Researchers at Yale School of Medicine have found that exaggerated responses of the immune system explain why the elderly succumb to viral infections more readily than younger people.
Thoughtful words help couples stay fighting fit
Couples who bring thoughtful words to a fight release lower amounts of stress-related proteins, suggesting that rational communication between partners can ease the impact of marital conflict on the immune system.
Researchers mobilizing global resources to test new treatments for severe H1N1 infection
An important, ground-breaking initiative is unfolding in the global critical care community in response to the H1N1 pandemic.
People with less education could be more susceptible to the flu
People who did not earn a high school diploma could be more likely to get H1N1 and the vaccine might be less effective in them compared to those who earned a diploma, new research shows.
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
UCI embryonic stem cell therapy restores walking ability in rats with neck injuries
The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.
Hundreds of genes distinguish patients likely to survive advanced melanoma
Although the chances of surviving advanced melanoma aren't very good with current therapies, some patients can live for years with cancer that has spread beyond the skin to other organs.
New Notre Dame study provides insights into the molecular basis of tumor cell behavior
A new study by a team of researchers led by Crislyn D'Souza-Schorey, associate professor of biological sciences at the University of Notre Dame, sheds light on the molecular basis by which tumor cells modulate their surroundings to favor cancer progression.
New Synthetic Molecules Trigger Immune Response to HIV and Prostate Cancer
Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in the Journal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.
More Immune Response Current Events and Immune Response News Articles
 |
Immune Response and the Eye (Chemical Immunology) by Jerry Y. Niederkorn (Editor), Henry J. Kaplan (Editor) In memory of J. Wayne Streilein, the pioneer in ocular immunology The second edition of Immune >Response and the Eye' highlights recent insights into the >dangerous compromise' between the immune system and the eye, which protects the eye against pathogens while limiting inflammation and immune-mediated injury to ocular tissues with little or no regenerative potential. It discusses the broad spectrum of physiological, immunological, anatomical, and biochemical adaptations that conspire to closely regulate the tone and tenor of immune responses in the eye. This volume further describes immune-mediated diseases that occur when the compromise between the immune system and the eye is breached. This breakdown in immune privilege threatens the vision of millions each year. Finally, recent... |
 |
Source Naturals Aller-Response, Tablets, 90 tablets (Pack of 2) by Source Naturals Dietary supplement. Quercetin, Ginkgo & Synephrine. Aller-Response is a seasonal formula featuring quercetin. Human cell culture studies with quercetin demonstrated its capability to inhibit the release of histamines. Ginkgolide B, in human cell culture s |
|
Understanding Hereditary Angioedema: A Mysterious Out-Of-Control Immune Response Directed By: Information Television Network | |
 |
Understanding Hereditary Angioedema: A Mysterious Out-of-Control Immune Response (Home Use) Part of the award winning public television series Healthy Body/Healthy Mind. Its called Hereditary Angioedema and its so rare popular television shows have used it as one of their mystery diagnoses. But for the people who suffer with this condition the drama associated with an episode of hereditary angioedema is anything but entertaining. It can be harrowing and horrifying because a person's face or knees or other parts of the body that once looked normal suddenly takes on grotesque proportions due to an unusual amount of swelling. This condition baffled scientists and researchers for many years but today there are new treatments for hereditary angioedema that are helping people with this condition live healthy normal lives. In this program we'll hear what the experts have discovered... |
 |
Chlamydia pneumoniae immunology: Innate Immune Responses induced by Chlamydia pneumoniae infection by Vjera Magdalenic (Author) Chlamydiae are common pathogens that cause a number of serious but preventable diseases in both humans and animals. In the recent years, Chlamydia pneumoniae has emerged as a major cause of human respiratory disease and more importantly, it has been linked to the establishment and exacerbation of serious chronic diseases including atherosclerosis and ischaemic heart disease, multiple sclerosis and reactive arthritis. There has been a lot of research into host responses to chlamydial infections and the development of immunopathology; but considerable gaps in our knowledge remain. The work described here aimed to analyse the early innate immune responses in the lung following C. pneumoniae infections with a view to better understanding host-pathogen interactions and the... |
 |
Vetri-DMG Tablets for Dogs & Cats (90 Tabs) by vetri science Vetri-DMG Tablets for Dogs & Cats (90 Tabs) (Supports Performance and Immune System Function) Vetri DMG is recommended to help support proper immune response, cardiovascular and skin health, glucose metabolism and proper nerve and brain functions. |
 |
Metabolic Maintenance L-Glutamine 500 mg 100 caps by Metabolic Maintenance L-Glutamine 500 mg 100 caps |
 |
Selected Aspects of Cancer Progression: Metastasis, Apoptosis and Immune Response (Cancer Growth and Progression) by Hans E. Kaiser (Author), Hans E. Kaiser (Editor), Aejaz Nasir (Editor) The processes of tumor metastasis, apoptosis and anti-tumor immune response are among the most complex yet rapidly advancing fields in the area of cancer research. This monogaph presents a comprehensive coverage of the recent advances in the various key concepts in these fundamental aspects of human cancer. It would be of particular interest to members of the cancer research community, especially those who are actively involved in the study of basic and translational aspects of human cancer. Specifically, this volume includes authentic subject reviews by leading experts on the following aspects: Control of tumor cell motility Role of tumor-cell adhesion and migration in organ-selective metastasis-formation Tumor heterogeneity in relation to invasion and metastasis and its... |
 |
Bedside Emergencies: Anaphylactic Shock (Volume 3) Also With: Concept Media (Primary Contributor) Describes the body's normal immune response and how it responds physiologically to allergens. Differentiates between anaphylactic and anaphylactoid reactions, describing signs and symptoms. Describes initial interventions to slow down or prevent reaction from becoming life-threatening, as well as more aggressive therapy for severe, progressive reactions. |
 |
Primer to The Immune Response by Tak W. Mak (Author), Mary Saunders (Author) Primer to The Immune Response is an invaluable resource for college students, university undergraduates and students in medicine and other health professions who need a concise but complete and understandable introduction to immunology. This book is written in the same engaging conversational style as the published reference book The Immune Response: Basic and Clinical Principles and conveys the same fascinating appeal of immunology. The authors bring clarity, readability and continuity of voice to an audience that requires only a brief survey of the most fundamental concepts in basic and clinical immunology. Primer to The Immune Response is beautifully illustrated with over 200 superb figures and 36 full color plates, and further enhanced by the inclusion of 60 tables and 6... |
| © 2009 BrightSurf.com |