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D Frasca

Publications and source records attributed to D Frasca.

At least 37 records · Page 2Linked to original sources
PubMed1998

Inhibition of IL-2 production by Nil-2-a in murine T cells.

The loss of IL-2 production is the main defect accounting for age-related immunodeficiencies. We have investigated the molecular mechanisms involved in the decrease of IL-2 production in CD4+ T cells from aging mice. Our results demonstrate that the stability of IL-2 mRNA increases in T cells from young mice, whereas it declines in T cells from old mice with the time of stimulation, suggesting the existence of different mechanisms of post-transcriptional regulation in young and old mice. We found that the IL-2 mRNA level in T cells from young but not from old mice increased up to 6- to 10-fold by addition of cycloheximide (CHX) while the stability of IL-2 mRNA is not affected. We then looked for IL-2 inducible inhibitory factors in T cells from young and old mice and demonstrated the presence of Nil-2-a, a zinc finger protein which negatively controls IL-2 gene transcription in human cells. This protein could be detected in T cells from both young and old mice, yet, in the presence of CHX, its binding activity was reduced by 75% in T cells from young but not from old mice. These findings show that Nil-2-a accounts for the negative control of IL-2 production in the mouse and explain the reduced IL-2 production in aging.

Age Factors↗
PubMed1998

Age-related propensity to peripheral expansion of Vgamma3+ gammadelta+ T lymphocytes after irradiation and bone marrow transplantation.

The age-related decline in T cell functions is generally considered to be due to changes in the responding alphabeta T cell populations as a result of impairment of T cell differentiation in the thymus. T cells bearing the gammadelta TCR are normally a minor subset of circulating T cells, but often the major T cell type among lymphocytes in epithelial tissues. In this paper we show that gammadelta T cells are expanded in lymph nodes of irradiated mice after syngenic bone marrow transplantation. Interestingly, these gammadelta T cells express mainly the Vgamma3 TCR, which is characteristic of dendritic epithelial T cells that can develop in athymic nude mice and may recognize self antigens. Since the peripheral expansion of Vgamma3 T lymphocytes is closely related to bone marrow age, these observations indicate that the age-related propensity to extrathymic development of Vgamma3+ gammadelta+ T lymphocytes is mainly due to stem cell dysregulation in aging. This phenomenon may contribute to T cell impairment and to the increased natural cytotoxic activity of lymphoid cells in aged mice.

Aging↗
PubMed1998

Psychoneuroimmunology and aging.

BACKGROUND: The senescence of the immune system is a complex phenomenon, characterized by impairment of several lymphocyte activities and generally considered a state of immune dysregulation. Aging is a condition associated with many social changes likely to induce psychological stress, which is often perceived as uncontrollable and can lead, in some cases, to clinically relevant depression. In the recent years a growing interest has been raised for the study of bidirectional interactions between the central nervous system and the immunological network (psychoneuroimmunology). OBJECTIVE AND METHODS: We analyzed the possibility that chronic psychological distress and depression could worsen some immune functions in the aged. We postulate the neuroendocrine mechanisms of psychoimmune interaction, analyzing both the human and animal studies focused on aging. RESULTS: The data from the literature reviewed suggest a significant impact of affective disorders on immune functions in the elderly subjects. This psychoimmune imbalance appears particularly important when the studies are carried out in otherwise healthy aged people. CONCLUSIONS: Here we reviewed the relationships between psychological stress and depression and immunological functions, with particular regard to those aspects pertinent to the aging process. The clinical relevance of these interactions remains to be elucidated, but the high frequency in the aged of autoimmune, infectious, and neoplastic diseases suggests to focus on the psychoneuroimmune interactions in the old age. We also propose some outlines for future studies concerning psychoneuroimmunology and aging.

Aging↗
PubMed1997

Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells.

We investigated the production of IL-2 and IFN-gamma (Th1 type) and IL-4 (Th2 type) cytokines by mitogen-activated spleen cells from young, adult and old mice. Cytokine production was evaluated in culture supernatants by CTLL proliferation (IL-2), ELISA (IFN-gamma), CT4.S proliferation (IL-4) and in mRNA extracted from activated CD4+ cells by RT-PCR (IL-2, IFN-gamma and IL-4). Results show that the production of IL-2, as protein and mRNA, is profoundly depressed by aging, whereas that of IFN-gamma, as protein and mRNA, firstly declines and then increases with age. The production of IL-4, as protein, monotonically declines with aging whereas, as mRNA, firstly decreases and then increases above the level in young mice. Spleen cells in culture were also incubated with mitogens and with a recombinant cytokine (IL-1 beta, IL-2, IL-3, IL-4, IL-12 or IFN-gamma) at various concentrations. It was found that recombinant cytokines by and large enhance cytokine production when the level induced by mitogens only is low. This conclusion applies to IL-2 and IFN-gamma production as protein and mRNA. The addition of recombinant cytokines also increases the production of IL-4 at the protein level in spleen cells from old mice but, at the mRNA level, only in spleen cells from young mice. This finding suggests age-related changes in IL-4-specific mRNA transcription rate and post-transcriptional half-life as well as translation kinetics.

Aging↗
PubMed1997

Aging of the recipients but not of the bone marrow donors enhances autoimmunity in syngeneic radiation chimeras.

Young and old mice have been lethally irradiated and injected with syngeneic bone marrow cells from young or old donors to investigate whether self reactivity in old mice results from age-related damage of the radioresistant stromal cells and/or of the bone marrow hematopoietic cells. Thymus and spleen cell repopulations and mitotic responses at 3 months after irradiation are lower in old than in young recipients, suggesting age-related accumulation of stromal cell damage in the thymus as well as in other central and peripheral lymphoid tissues. The same efficiency of bone marrow cells from young and old donors to repopulate the thymus and spleen in recipients of equal age rules out the detrimental effects of aging on stem cells as well as T and B cell precursors. The serum concentration of auto-antibody and glomerular lesions at 3 and 9 months after irradiation were more pronounced in old than in young recipients and displayed no difference in recipients of equal age, regardless of the age of the bone marrow cell donors. These findings support the possibility that age-related damage of stromal cells induces disregulation of the immune system leading to autoimmune phenomena.

Aging↗
PubMed1997

Genes, immunity, and senescence: looking for a link.

Aging is under the control of a small number of regulatory genes. Mice genetically selected for high immune responses, in most cases, exhibit longer life span and lower lymphoma incidence than do mice selected for low responses. The link between immunity and aging is further evidenced by the age-related alterations of the immune system, mostly of the T-cell population, in terms of replacement of virgin by memory cells, accumulation of cells with signal transduction defects, and changes in the profile of Th1 and Th2 type cytokines. Also, B cells exhibit intrinsic defects, and natural killer (NK) cell activity is profoundly depressed by aging. In vitro experiments indicate that IL-2, IFN-gamma, and IL-4 production by mouse spleen cells changes with aging and may be upregulated by recombinant cytokines. These findings suggest possible cytokine interventions to prevent or treat age-related immune disorders, as they may affect the duration and the biological quality of life.

Aging↗
PubMed1997

Use of hematopoietic cytokines to accelerate the recovery of the immune system in irradiated mice.

In our previous studies aimed at designing appropriate strategies to accelerate recovery of the immune system after irradiation, we found that the hematopoietic cytokine recombinant murine (rmu) interleukin (IL)-3 was able to induce differentiation and growth of thymocytes and splenic T and B lymphocytes in mice exposed to x-rays (200-500 cGy). The recovery, however, was complete at 7 days only after a dose of 200 cGy, whereas 2, 3, and 4 weeks were necessary to achieve full recovery after 300, 400, and 500 cGy, respectively. These studies were extended to investigate the effects of another hematopoietic cytokine, recombinant human (rhu) IL-11, a bone marrow stromal-derived cytokine, administered together with IL-3 to irradiated mice. The synergistic effect of the two cytokines was evident when relatively small doses of rhu IL-11 were injected with an optimal dose of rmu IL-3.

Animals↗
PubMed1996

IL-11 synergizes with IL-3 in promoting the recovery of the immune system after irradiation.

In our previous studies aiming at the design of appropriate strategies to accelerate the recovery of the immune system after irradiation, we found that recombinant murine (rmu) IL-3 treatment induces differentiation and growth of thymocytes and splenic T and B lymphocytes in mice exposed to X-rays (200-500 cGy). These studies were extended to investigate the effects of recombinant human (rhu) IL-11. Results indicate that rhuIL-11 is able to restore thymus and spleen cell numbers as well as T and B cell mitotic responsiveness in mice exposed to 200 cGy but not to 300 cGy. However, recovery of thymus and spleen cell numbers and functions could be accelerated also in mice exposed to higher dose if rhuIL-11 was given with rmuIL-3. Recovery was complete as soon as 7 days after irradiation. A large dose of both cytokines was explored and the synergistic effect of the two cytokines was evident when a relatively small dose of rhuIL-11 was injected with graded doses of rmuIL-3. The recovery of the immune system in irradiated mice injected with these cytokines was independent from Bcl-2 expression, suggesting that elimination of damaged cells by apoptosis is unaffected by hematopoietic cytokines.

Animals↗
PubMed1996

Hormone replacement therapy affects various immune cell subsets and natural cytotoxicity.

The effects of hormone replacement therapy (HRT) on lymphocytes and granulocytes have never been determined in detail. Ten healthy menopausal women (age 49-51 years; menopause less than 2 years) were treated for 6 months by administering transdermal estradiol (100 micrograms/day for 21 consecutive days) and oral medroxyprogesterone acetate (10 mg/day from day 10 to day 21). Days 22-28 were therapy-free. All subjects were examined during the first and the last month of treatment: evaluations were carried out on days 0, 8, 21 and 28. CD4+CD45RO+ cells were found to be significantly reduced on day 8. CD56+ cells and CD8+CD11b+ cells were decreased on day 21 and recovered basal level on day 28. Natural killer cell function was transiently increased on day 8 and greatly reduced on day 21. During the first month of therapy, the expression of Leu8 and CD11b antigens on granulocyte membranes was significantly affected by HRT. Taken together, the results indicate that HRT selectively affects various immune cell subsets.

Cytotoxicity, Immunologic↗
PubMed1994

Murine recombinant interleukin-3 induces recovery of T and B cells in irradiated mice.

Injection of murine recombinant interleukin-3 (IL-3) into (C57BL/10 x DBA/2)F1 mice, sublethally irradiated with 300 cGy and killed 14 days later, induced in the thymus recovery of the cell number and mitotic responsiveness to concanavalin A (Con A), as well as an increase in number of double-negative CD4-CD8-, double-positive CD4+ CD8+, and single-positive CD4+CD8- and CD4-CD8+ cells. Also in the spleen, the cell count and mitotic responsiveness to Con A and lipopolysaccharide were increased to normal levels by IL-3 treatment. If the assays were performed 21 or 28 days after irradiation, IL-3 treatment was able to restore thymus and spleen cell counts as well as T- and B-cell mitotic responsiveness, even when mice were exposed to 400 or 500 cGy, respectively. These results altogether indicate that IL-3 induces differentiation and growth of thymocytes and recovery of T- and B-cell functions in mice exposed to sublethal irradiation.

Animals↗
PubMed1994

Ageing and genetic control of immune responsiveness.

Ageing is associated with a progressive decline of immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focussed on the mechanisms of the immunologic features of ageing. Alterations in cellular components of the immune system rather than in the extracellular milieu seem to account for most of the variations of immune competence in ageing.

Aging↗
PubMed1993

Effect of recombinant IL-3 on lymphocyte populations in irradiated mice.

Administration of murine recombinant interleukin 3 (IL-3) to sublethally irradiated mice induced in the thymus recovery of the cell count and mitotic responsiveness to Con A, as well as a decrease in CD4-CD8- cells concomitant with an increase in single positive cells. Also in the spleen, the cell count and mitotic responsiveness to Con A and lipopolysaccharide (LPS) were recovered by IL-3 treatment. These findings show that IL-3 induces differentiation and growth of thymocytes and recovery of T and B cell functions in sublethally irradiated mice.

Animals↗