0000000000193141
AUTHOR
Alessandra Aquino
Regulatory T cells and ageing
CD4+ / CCR5+ and CD4+ / CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis
A study of serum immunoglobulin levels in elderly persons that provides new insights into B cell immunosenescence.
The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, we investigated the serum immunoglobulin levels in a cohort of 166 subjects (20-106 years). Serum IgG (and IgG subclasses) were quantified by the nephelometric technique, IgE by CAP system fluorescence enzyme immunoassay, and IgD by radial immunodiffusion (RID). There was an age-related increase of IgG and IgA; the IgG age-related increase was significant only in men, but IgG1 levels showed an age-related increase both in men and women, whereas IgG3 showed an age-related increase only in men. IgE levels remain unchanged, whereas IgD and IgM serum levels d…
B cell immunosenescence in the elderly and in centenarians.
The elderly suffer from an increased susceptibility to infectious disease and cancer. Aging of the immune system contributes to this state of affairs due to immunosenescence. Because repeated intermittent or chronic antigen exposure may lead to lymphocyte clonal exhaustion, chronic antigenic stress plays a part in the compromised immunity of the elderly, who have accumulated a lifetime's exposure to infectious agents, autoantigens, and cancer antigens. Literature on immunosenescence has focused mainly on T cell impairment, but B cell compartment is also affected. The age-dependent B cell changes documented by the present review indicate that advanced age per se is a condition characterized …
B CELL IMMUNOSENESCENCE IN THE ELDERLY
Looking for Immunological Risk Genotypes
Several functional markers of the immune system may be used either as markers of successful aging or conversely as markers of unsuccessful aging. Particularly, a combination of high CD8 and low CD4 and poor T cell proliferation has been associated with a higher two-year mortality in very old subjects. Therefore, genetic determinants of longevity should reside in those polymorphisms for the immune system genes that regulate immune responses. Concerning these changes in T cell subpopulations, how much they depend on the immunogenetic background and how much they depend on individual antigenic load, such as chronic infections, should be assessed. As previously demonstrated in our population, t…
Gamma/delta T lymphocytes are affected in the elderly
gammadelta T lymphocytes are considered to represent a link between the inflammatory response and adaptive immunity. In the present paper we investigated whether these cells play any role in the remodeling of the immune system described in the elderly. We show that the absolute number of gammadelta T cells in peripheral blood of old and very old subjects is reduced. Moreover, gammadelta T cells from old people and centenarians show enhanced levels of the early activation marker CD69 both after culture in medium alone and in LPS-stimulated cells. Furthermore, they show a basal increased production of tumor necrosis factor (TNF)-alpha as evaluated at the single cell level. Additionally, the r…
Memory B Cell Subpopulations in the Aged
The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, the authors investigated the serum IgD levels in 24 young and 21 old people and analyzed their relationship with the number of CD19 CD27 memory cells. Serum IgD were quantified by the use of radial immunodiffusion and the lymphocyte population CD19 CD27 was identified by a FACScan flow cytometer. Serum IgD levels were significantly lower (p 0.0001) in old subjects, and the percentage of CD19 CD27 lymphocytes were significantly increased (p 0.01) in old subjects. Finally, a significant negative correlation was found (p 0.01) between serum concentrations of…
REGULATORY T CELLS IN FRAIL ELDERLY
Inflammation, longevity and cardiovascular diseases: role of polymorphisms of TLR4
CITOCHINE. in: Compendio di Patologia generale (Caruso C. e Licastro F. eds.)
Antigeni, anticorpi, TCR
CD4+CD25+ regulatory cells in aged people are related to IL-10 genetic background and have effect on CMV-specific CD8 lymphocytes
Le cellule T regolatrici CD4+CD25+ negli anziani sono correlate al background genetico dell’Il-10 ed hanno effetti sui linfociti CD8-CMV specifici
Memory B cells in aged
CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis
The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expres…
Familial mediterranean fever, longevity and cardiovascular diseases: a pilot study in the Sicilian population
Inflammation, Longevity, and Cardiovascular Diseases: Role of Polymorphisms of TLR4
The total burden of infection at various sites may affect the progression of atherosclerosis, the risk being modulated by host genotype. The role of lipopolysaccaride receptor TLR4 is paradigmatic. It initiates the innate immune response against gram-negative bacteria; and TLR4 polymorphisms, as ASP299GLY, suggested to attenuate receptor signaling, have been described. We demonstrated that TLR4 ASP299GLY polymorphism shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians show a higher frequency. Thus, people genetically predisposed to developing weak inflammatory activity, seem to have fewer chances of developing cardio…
Valutazione Dei Linfociti T Regolatori CD4+CD25+ (Treg) Nell’anziano
B cells in the aged: CD27, CD5, and CD40 expression.
Ageing is characterized by numerous changes in lymphocyte subpopulations. In the present paper we have focused on B cells carrying the surface markers CD27, CD5 and CD40. CD27 is considered a marker of primed (memory) cells and its engagement promotes the differentiation of memory B cells into plasma cells. CD5 is expressed on B1 cells, which are considered to be responsible for T cell-independent antibody production other than autoantibodies. The CD40 molecule binds CD40L (CD154) and is necessary for T-dependent antibody responses. Here we show that the absolute number of CD5+ and CD40+ B cells is decreased in the elderly, while CD27+ B lymphocytes only marginally decrease in centenarians.…
CITOCHINE
Impairment of gamma/delta T lymphocytes in elderly: implications for immunosenescence
Gamma/delta T lymphocytes cells recognize the antigen in a non-classical way and are considered the third branch of the immune system devoted to defend the integrity of the body. Ageing is characterized by an impairment of the main way of protection (the adaptive branch) but, successfully aged people show compensatory mechanisms of defense such as proneness to inflammation. Moreover, very old subjects show an increased number of NK cells. We have previously demonstrated that gamma delta T lymphocytes are reduced in elderly. In the present paper we have studied some characteristics of these cells to evaluate the possibility that these cells might balance the decreased action of the adaptive …
Impact of CMV and EBV seropositivity on CD8 T lymphocytes in an old population from West-Sicily.
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…
The nACHR4 594C/T polymorphism in Alzheimer disease
Alzheimer disease (AD) is the most common form of dementia with complex etiology and multifactorial origin. Although several neurochemical deficits have been described in AD patients, explanation of the nature of the cognitive disturbance is focused on the "cholinergic hypothesis." The neuronal nicotinic acetylcholine receptor (neuronal nAChR) belongs to the superfamily of ionic channel activated by ligand. This paper presents a population-based population association study, testing the hypothesis that variants of the nAChR gene confer genetic susceptibility to AD. The authors analyzed two cohorts constituted by 60 controls and 80 AD patients in which significant increase of 594T polymorphi…
Linkage of HFE with HLA antigens: a study in Sicilian population.
A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people
The T cell branch of the immune system has been extensively studied in the elderly and it is known that the elderly have impaired immune function, mainly due to the chronic antigenic load that ultimately causes shrinkage of the T cell repertoire and filling of the immunologic space with memory T cells. In the present paper, we describe the IgD(-)CD27(-) double-negative B cell population which (as we have recently described) is higher in the elderly. Most of these cells were IgG(+). Evaluation of the telomere length and expression of the ABCB1 transporter and anti-apoptotic molecule, Bcl2, shows that they have the markers of memory B cells. We also show that these cells do not act as antigen…