0000000000041555
AUTHOR
Maria Assunta Modica
In Vitro Cytokine Production by HLA-B8, DR3 Positive Subjects
It is well known that healthy subjects carrying the HLA-B8,DR3 haplotype may show an impairment of immune system, the T cells being the most affected. To gain insight into the mechanism(s) of the impairment displayed by these subjects, efforts have been centered on the study of in vitro cytokine production because of the pivotal role played by these mediators in the activation and control of several immune functions. The available results indicate that the ability to several immune functions. The available results indicate that the ability to produce interleukin-1 (IL-1), IL-2 and the soluble form of its receptor (sIL-2R) is impaired in HLA-B8,DR3 positive healthy subjects. To better charac…
The effect of age on mitogen responsive T cell precursors in human beings is completely restored by interleukin-2.
Abstract It is well known that the function of T lymphocytes is significantly impaired by advancing age. In the present study, attempts have been made to further characterize the T cell impairment of elderly subjects. Thus, we have performed limiting dilution microculture analysis to evaluate the precursor frequency of T lymphocytes responding to a mitogenic stimulus in old and young subjects. Furthermore we have evaluated the activity of recombinant interleukin-2 (rIL-2) on these cells. The results demonstrate that in older subjects the frequency of these precursors is significantly decreased. The in vitro treatment with rIL-2 increased the frequency of mitogen responsive T lymphocyte prec…
Soluble Interleukin-2 Receptor Secretion Defectin Vitroin HLA-B8, DR3 Positive Subjects
Several studies have shown that HLA-B8,DR3 positive subjects may display T cell dysfunctions. Recently, a soluble form of the receptor for IL-2 (sIL-2R) has been demonstrated in human sera and in vitro-stimulated culture supernatant from human T lymphocytes. In the present paper we report sIL-2R serum levels and sIL-2R production from peripheral blood mononuclear cells in HLA-B8,DR3 positive subjects. We found that HLA-B8,DR3 positive subjects have the highest values of serum sIL-2R, but comparing the values of these subjects with those of negative ones no significant difference was observed. As regards the in vitro production of sIL-2R, no difference exists for unstimulated cultures, where…
HLA-B8,DR3 phenotype and lymphocyte responses to phytohaemagglutinin.
Several reports have shown that HLA-B8,DR3 positive subjects may display some changes in immune parameters when compared with HLA-B8,DR3 negative ones and are prone to develop several immunological diseases. In the present study we have analysed the proliferative response to phytohaemagglutin (PHA) in HLA-typed healthy subjects. A twin method was also employed to assess the role of genetic and environmental factors in the regulation of the response to the mitogen. It was not possible to demonstrate any difference in proliferative response to optimal doses of PHA between groups of subjects carrying or not carrying the HLA-B8,DR3 phenotype. When suboptimal responses were studied, however, the…
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…
Markers of T Lymphocyte Activation in HLA-B8, DR3 Positive Individuals
Many autoimmune diseases are associated in Caucasians with HLA-B8 and/or HLA-DR3 antigens. There is evidence that bearers of these antigens may display significant changes in immune parameters when compared to individuals not having these antigens. Recently, increased numbers of blood activated T lymphocytes have been reported in the majority of these diseases. The increase in activated blood T lymphocytes is paradoxically characterized by an in vitro impairment of T cell activation. Particularly, an inadequate production of interleukins has been observed. We have studied blood levels of activated T cells in HLA-typed, healthy subjects. The results show that the percentage of activated T ce…
Major histocompatibility complex regulation of cytokine production.
This review describes the phenomenon of the major histocompatibility complex (MHC) control of cytokine production both in experimental animals and in humans. H-2 (mouse MHC) regulates which type of cytokine is selectively produced in response to the hapten trinitrophenyl (TNP). T cells from TNP-immune H-2k mice produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-3, IL-5, tumor necrosis factor-alpha (TNF-alpha), IL-10, and very low levels of IL-4 on reexposure to the specific antigen in vitro. By contrast, T cells from H-2d mice produce IL-3, TNF-alpha, IL-10, and IL-4 but very low levels of IL-2, IL-5 and IFN-gamma. As MHC-congenic matched strains (BALB/k and BALB/c) are used, th…
Hla-Bb, Dr3 T Cell Impairhent is Completely Restored by in Vitho Treatment with Interleukin-2
AbstractThe activity of recombinant interleukin-2 (rIL-2) on the in vitro lymphocyte proliferative response to phytohemagglutinin mitogen was investigated in healthy HLA-BB, DR3 positive and negative subjects. the response to mitogen, significantly decreased in HLA-BB, DR3 positive subjects, was completely restored by adding rIL-2. Moreover, in HLA-BB, DR3 positive subjects the in vitro treatment with rIL-2 significantly increased the reduced frequency of mitogen responsive T lymphocyte precursors, as assessed by limiting dilution analysis. These data suggest that a decrease in the size of the pool of T cell precursors able to produce IL-2 is responsible for the impairment of T cell functio…
Interleukin 2 and soluble interleukin 2-receptor secretion defect in vitro in newly diagnosed type I diabetic patients
In this study, we investigated whether an interleukin 2 (IL-2) secretion defect by peripheral blood mononuclear cells (PBMCs) after in vitro stimulation with phytohemagglutinin (PHA-M) occurs in either newly diagnosed or long-standing type I (insulin-dependent) diabetic patients and whether it is accompanied by a dysregulation of soluble IL-2— receptor (IL-2RS) production. PBMC cultures (2.5 × 106 cells), unstimulated or stimulated with PHA-M (25 μg/ml), from 20 type I diabetic patients (10 with time since onset <3 mo and 10 with long-term diabetes of <3 yr) and 10 control subjects were studied for the production of IL-2 and IL-2RS in their respective supernatants. No differen…
Natural killer and lymphokine-activated killer activity in HLA-B8,DR3-positive subjects.
Abstract The haplotype HLA-B8,DR3 is over-represented in several autoimmune diseases, implying that genes predisposing people to these disorders are linked to this haplotype. In these diseases, various dysfunctions reflecting an impairment of the immune system have been found. Several reports indicate also that in HLA-B8,DR3-positive healthy subjects similar disorders may be demonstrated. In the present work, we have evaluated NK and LAK activity in these subjects. The study has been performed on monocyte-depleted peripheral blood MNCs by using the K-562 cell line as a target for NK activity and the HL-60 cell line for as a target LAK activity. LAK cells were obtained by incubating MNCs for…
HLA-Cw4 Association with Acute Lymphoblastic Leukaemia in Sicilian Patients
The HLA frequencies of 50 Sicilian patients affected with acute lymphoblastic leukaemia (ALL) were examined. The frequency of Cw4 antigen was significantly increased in patients. Thus results obtained in our homogeneous population confirm in part previous reports suggesting that Cw4-related genetic factors might be involved in the susceptibility to aetiological or pathogenetic mechanisms which play a role in some haematological malignancies.
Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: a genetically determined defect of C4 influences immunological parameters of healthy carriers of the haplotype.
Abstract Subjects with certain HLA alleles have a higher risk of specific autoimmune diseases than those without these alleles. The 8.1 ancestral haplotype (AH) is a common Caucasoid haplotype carried by most people who type for HLA-B8,DR3. It is unique in its association with a wide range of immunopathological diseases. To gain insight into the identification of the mechanism(s) of disease susceptibility of 8.1 AH carriers, we have investigated the prevalence of circulating immune complexes and non-organ-specific autoantibodies in healthy carriers of the haplotype. The results show that carriers of 8.1 AH display both a significant increased prevalence of immune complexes and higher titers…
Biological Basis of the HLA-B8,DR3-Associated Progression of Acquired Immune Deficiency Syndrome
The factors influencing the evolution of human immunodeficiency virus (HIV) infection are not fully known, but the host genotype undoubtedly plays a role in determining the outcome of the disease by affecting the immune response to HIV. The role of the host human leukocyte antigen (HLA) genotype in the regulation of susceptibility to HIV infection and expression has been studied extensively in different major risk groups. Certain HLA alleles and haplotypes, being associated with aberrant immune responses independently from HIV infection, have been reported to facilitate the rapid progression of disorders related to HIV infection. Particularly, the association of rapid acquired immunodeficie…
gamma-Interferon, interleukin-4 and interleukin-6 in vitro production in old subjects.
It is well known that ageing is associated with various alterations of the lymphoid cell functions. Although both B and T cell are affected, the last appear to be more sensitive to ageing process. During the past years, to gain insight into thé mechanism(s) of this impairment, effort has been centered on the helper T cells specifically engaged in the production of interleukin-2 (IL-2) because of the pivotal role played by this cytokine in the activation of several immune functions. The results have demonstrated that the ability to produce IL-2 declines with age. In this paper we report the results of a study performed to determine the influence of age on the capacity to produce gamma-interf…