0000000000958204
AUTHOR
Graham Pawelec
showing 18 related works from this author
A novel B cell population revealed by a CD38/CD24 gating strategy: CD38−CD24− B cells in centenarian offspring and elderly people
2012
The B cell arm of adaptive immunity undergoes significant modifications with age. Elderly people are characterized by impaired B cell responses reflected in a reduced ability to effectively respond against viruses and bacteria. Alterations of immunity with advancing age (immunosenescence) have been widely studied in centenarians who are considered a good example of successful aging. In recent years, attention has shifted to centenarian offspring (CO) as a model of people genetically advantaged for healthy aging and longevity. Here, we describe the preliminary characterization of a proposed new population of memory B cells, defined as CD19(+)CD38(-)CD24(-), which we find at higher frequencie…
Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes☆
1999
Abstract Aging is associated with alterations of the immune system, thought to be related to an increased susceptibility to infectious diseases, and possibly to cancer and autoimmunity in the elderly. In the present paper we report data obtained on freshly collected blood from 148 healthy subjects of different ages (from cord blood to 102 years old). The subjects were divided into seven age classes (cord blood, 3–11 years, 15–39 years, 41–60 years, 61–74 years, 75–84 years, 85–102 years) and their lymphocyte subsets and the expression of the apoptosis-related molecule CD95 were evaluated. In respect of lymphocyte subsets, the major differences were found in the cord-blood samples compared w…
'Immunogenetics of Aging': report on the activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Imm…
2011
'Immunogenetics of Aging' is a component that was first included in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th Workshop. The aim of this component was to assess the impact of human leukocyte antigen (HLA) genes, cytokine genes, and some innate immunity genes such as killer-cell immunoglobulin-like receptors (KIRs) and mannose-binding lectin 2 (MBL2) in successful aging and their contribution to the better understanding of immune dysfunction in old age. Within the 15th IHIWS new populations were included in the analysis. Additional cytokine gene polymorphisms were assessed and innate immunity genes were analyzed for possible relevance…
Age and immunity
2006
Abstract Longitudinal studies are defining progressive alterations to the immune system associated with increased mortality in the very elderly. Many of these changes are exacerbated by or even caused by chronic T cell stimulation by persistent antigen, particularly from Cytomegalovirus. The composition of T cell subsets, their functional integrity and representation in the repertoire are all markedly influenced by age and by CMV. How these findings relate to epidemiological, functional, genetic, genomic and proteomic studies of human T cell immunosenescence was the subject of intense debate at an international conference held just before Christmas 2005 in the Black Forest.
Report from the second cytomegalovirus and immunosenescence workshop
2011
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.; International audience; The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vacc…
Role of persistent CMV infection in configuring T cell immunity in the elderly
2007
Abstract Ageing is associated with declines in many physiological parameters, including multiple immune system functions. The rate of acceleration of the frequency of death due to cardiovascular disease or cancer seems to increase with age from middle age up to around 80 years, plateauing thereafter. Mortality due to infectious disease, however, does not plateau, but continues to accelerate indefinitely. The elderly commonly possess oligoclonal expansions of T cells, especially of CD8 cells, which, surprisingly, are often associated with cytomegalovirus (CMV) seropositivity. This in turn is associated with many of the same phenotypic and functional alterations to T cell immunity that have b…
T cell assays and MIATA: the essential minimum for maximum impact.
2012
The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA*Correspondence: cedrik.britten@tron-mainz.dehttp://dx.doi.org/10.1016/j.immuni.2012.07.010The field of immunology has recentlyexperienced enormous advances fromwhich most have so far not been incorpo-rated into standard medical practice (Da-vis, 2008). One approach to fully exploitthe existing wealth of knowledge is toimplement a systematic strategy to eval-uate the immune system. The potentialbenefit of such an approach is that itmay lead to results that can be translatedinto the rational development of diagnos-tics and therapeutics (Hoos et al., 2011).Two prerequisites for its application ar…
Mechanisms of immunosenescence
2009
Abstract On April 7,8, 2009 a Symposium entitled "Pathophysiology of Successful and Unsuccessful Ageing" took place in Palermo, Italy. Here, the lectures of G. Pawelec, D. Dunn-Walters and. G. Colonna-Romano on T and B immunosenescence are summarized. In the elderly, many alterations of both innate and acquired immunity have been described. Alterations to the immune system in the older person are generally viewed as a deterioration of immunity, leading to the use of the catch-all term immunosenescence. Indeed, many immunological parameters are often markedly different in elderly compared to young people, and some, mostly circumstantial, evidence suggests that retained function of both innat…
Evidence for Less Marked Potential Signs of T-Cell Immunosenescence in Centenarian Offspring Than in the General Age-Matched Population
2014
People may reach the upper limits of the human life span at least partly because they have maintained more appropriate immune function, avoiding changes to immunity termed "immunosenescence." Exceptionally long-lived people may be enriched for genes that contribute to their longevity, some of which may bear on immune function. Centenarian offspring would be expected to inherit some of these, which might be reflected in their resistance to immunosenescence, and contribute to their potential longevity. We have tested this hypothesis by comparing centenarian offspring with age-matched controls. We report differences in the numbers and proportions of both CD4(+) and CD8(+) early- and late-diffe…
Immune profiling of Alzheimer patients
2011
Abstract Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4 + rather than the CD8 + T cell compartment resulting in lower proportions of naive cells, more late-differentiated cells and higher percentages of activated CD4 + CD25 + T cells without a Treg phenotype in AD patients. Changes to CD4 + cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the dis…
Human immunosenescence: is it infectious?
2005
Morbidity and mortality due to infectious disease is greater in the elderly than in the young, at least partly because of age-associated decreased immune competence, which renders individuals more susceptible to pathogens. This susceptibility is particularly evident for novel infectious agents such as in severe acute respiratory syndrome but is also all too apparent for common pathogens such as influenza. Many years ago, it was noted that the elderly possessed oligoclonal expansions of T cells, especially of CD8(+) cells. At the same time, it was established that cytomegalovirus (CMV) seropositivity was associated with many of the same phenotypic and functional alterations to T-cell immunit…
Immunosenescence and Cytomegalovirus
2010
Since Looney at al. published their seminal paper a decade ago [1] it has become clear that many of the differences in T cell immunological parameters observed between young and old people are related to the age-associated increasing prevalence of infection with the persistent β-herpesvirus HHV-5 (Cytomegalovirus). Ten years later, studies suggest that hallmark age-associated changes in peripheral blood T cell subset distribution may not occur at all in people who are not infected with this virus [[2]; Derhovanessian et al., in press]. Whether the observed changes are actually caused by CMV is an open question, but very similar, rapid changes observed in uninfected patients receiving CMV-in…
Is immunosenescence infectious?
2004
Abstract Herpes viruses are endemic. Once established, the virus is never eliminated but persists throughout life. The fraction of infected individuals gradually increases with age, such that the majority of elderly people are cytomegalovirus (CMV) + , Epstein–Barr virus (EBV) + and Varicella + . Clinically relevant reactivation of Varicella causes painful shingles; CMV reactivation can cause fatal pneumonia. Overt reactivation, even in the very elderly, occurs only in immunocompromised individuals; however, the necessity for maintaining immunity to these viruses is costly. We argue that this cost is not only reflected in the requirement for continuous immunosurveillance against these virus…
Is human immunosenescence clinically relevant? Looking for ‘immunological risk phenotypes’
2002
Abstract The 3rd ImAginE Conference on ‘Basic Biology and Clinical Impact of Immunosenescence' was held at Palermo University, Italy from 10–13 April 2002.
Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers
2011
Abstract Purpose: To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of antitumor immunity to measure and which assays are optimal for those measurements. Experimental Design: The iSBTc-SITC (International Society for Biological Therapy of Cancer-Society for Immunotherapy of Cancer), FDA (Food and Drug Administration), and NCI (National Cancer Institute) partnered to address these issues for immunotherapy of cancer. Here…
Impact of CMV and EBV seropositivity on CD8 T lymphocytes in an old population from West-Sicily.
2007
Abstract Herpes viruses (particularly CMV and to some extent EBV) might play a role in accelerating the deterioration of immune functions with age. Indeed, it has been demonstrated that chronic infection with CMV causes an expansion of specific CD8 T lymphocytes and that this is related to a shrinkage of the T cell repertoire in very elderly people, predicting mortality. We have analysed CD8 T cells in young and old healthy Sicilians who were both CMV- and EBV-seropositive. Our data confirm expansions of T cells specific for the HLA-A2-restricted pp65 (495–503) CMV epitope up to nearly 14% of total peripheral CD8 cells in certain elderly individuals (range 0–14%). However, the mean percenta…
Vaccination in old age: Challenges and promises
2021
Abstract Vaccination is one of the most effective medical interventions ever introduced, preventing millions of cases of infections worldwide every year. However, vaccines are commonly believed to be less effective in providing protection in older adults, due to the perceived decline seen in immunity in this population (“immunosenescence”). Accordingly, this chapter considers how to identify hallmarks of immunosenescence and approach their resolution strategically. It was reviewed potential options for therapeutic intervention to restore appropriate responses to vaccines in older adults.
Aging and chronic inflammation: highlights from a multidisciplinary workshop
2023
Abstract: Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. Aging entails changes in the immune system characterized by a decrease in thymic output of naïve lymphocytes, an accumulated chronic antigenic stress notably caused by chronic infections such as cytomegalovirus (CMV), and immune cell senescence with acquisition of an inflammatory senescence-associated secretory phenotype (SASP). For this reason, and due to the SASP originating from other tissues, aging is commonly accompanied by low-grade chronic inflammation, termed “inflammaging”. After decades of accumulating evide…