Biomedical subjects

Nadzieja Drela

Publications and source records attributed to Nadzieja Drela.

8 recordsLinked to original sources

PubMed2006

CD28 in thymocyte development and peripheral T cell activation in mice exposed to suspended particulate matter.

The CD28:B7 signaling pathway is very important for the activity of mature peripheral T lymphocytes and thymocyte development. The proper development of thymocytes into mature single positive CD4+and CD8+ T cells is crucial for almost all immune functions. In naturally occurring conditions, T cells maturation in the thymus is influenced by environmental agents. The expression of CD28 and the distribution of CD28(low/high) thymocytes have been examined at various stages of thymocyte development in BALB/c mice exposed to air-suspended particulate matter (ASM). Acute exposure to ASM resulted in the decrease of CD28 expression in the total thymocyte population. The increase of the percentage of CD28(low) and the decrease of CD28(high) thymocytes were observed, which may account for the acceleration of thymocyte development under the conditions of elevated risk resulting from the exposure of animals to environmental xenobiotics. ASM exposure resulted in the increase of the level of proliferation of lymph node T cells induced by anti-CD3 and anti-CD28 monoclonal antibodies activation despite normal expression of CD28 molecule. In contrast, the level of proliferation of spleen T cells was lowered or normal dependently of the concentration of stimuli used for activation. Results of these studies demonstrate that acute exposure of mice to ASM can result in the progression of two contrasting processes in the immune system: upregulation of thymocyte development, which contributes to the maintenance of peripheral T cell pool, and over-activation of lymph node lymphocytes, which may lead to uncontrolled immunostimulation.

Air Pollutants↗

PubMed2006

Xenobiotic-induced alterations in thymocyte development.

The thymus is a very sensitive target for environmental pollutants, which can affect this organ as well as thymocyte differentiation. A failure in thymocyte development can be due to the exacerbation of apoptosis, arrest of thymocyte maturation, generation of autoreactive T cells, and inhibition or stimulation of the output of recent thymic emigrants to the periphery. Recent data demonstrate that the immune system has the potential to maintain homeostasis under conditions of elevated risk, and the thymus plays a crucial role in this process. Environmental xenobiotics can exert their effects through receptor-mediated interactions or independently on receptor involvement. Under natural conditions organisms are exposed to a variety of xenobiotics. The final effect of such exposure is not related to the action of a single chemical, but to the action of a mixture of chemicals. The toxic effect of environmental xenobiotics on the generation and functions of immune cells may result in suppression or stimulation of the immune response. The most intensive studies have been done on halogenated aromatic hydrocarbons, heavy metals and various chemicals acting as endocrine disrupters. Recently, special interest has focused on the action of air particulate matter.

Animals↗

PubMed2005

T-cell homeostasis in mice exposed to airborne xenobiotics.

Many effects of environmental toxic agents contribute to the deregulation of immune system homeostasis. Here we demonstrate that the effect of airborne suspended matter (ASM) on the generation of mouse T cells is reversible. This reversal can be achieved by an active process that returns the T cells to homeostasis and does not result from the simple effect of ASM deprivation. An accelerated development of thymocytes and increased influx of T-cell progenitors to the thymus in mice exposed to environmental xenobiotics has been postulated. This hypothesis has been confirmed by parallel increases in the percentages of single-positive and triple-negative thymocytes. Enhanced expression of thymocyte surface markers related to positive selection has also been observed. The pathway of T-cell progenitor development is favoured in the bone marrow of mice exposed to ASM.

Air Pollutants↗

PubMed2004

Moderate exercise may attenuate some aspects of immunosenescence.

BACKGROUND: Immunosenescence is related to the deterioration of many immune functions, which may be manifested in increased susceptibility to infection, cancer, and autoimmunity. Lifestyle factors, such as diet or physical activity, may influence the senescence of the immune system. It is widely accepted that moderate physical activity may cause beneficial effects for physical and psychological health as well as for the immune system activity in aged people. METHODS: Thirty elderly women aged 62 to 86 were subjected to a two-years authorized physical activity program. Peripheral blood lymphocytes distribution and the production of cytokines involved in the immune response development and regulation (IL-2, IL-4 and IFN-gamma) were investigated. The same parameters were evaluated in two control groups of women: a sedentary group of 12 elderly women selected for the second round of the physical activity program and in a group of 20 sedentary young women. Flow cytometry methods were used for the examination of surface markers on peripheral blood lymphocytes and intracellular cytokines expression. RESULTS: The distribution of the main lymphocytes subpopulations in the peripheral blood of elderly women did not show changes after long-term moderate physical training. The percentage of lymphocytes expressing intracellular IL-2 was higher in the group of women attending 2-years physical activity program than in the control group of elderly sedentary women, and it was similar to the value estimated in the group of young sedentary women. There was no difference in the intracellular expression of IL-4 and IFN-gamma between the active and elderly sedentary women. CONCLUSIONS: Our results suggest that moderate, long-term physical activity in elderly women may increase the production of IL-2, an important regulator of the immune response. This may help ameliorate immunosenescence in these women.

Journal Article↗

PubMed2004

CpG immunostimulatory oligodeoxynucleotide 1826 enhances antitumor effect of interleukin 12 gene-modified tumor vaccine in a melanoma model in mice.

PURPOSE: The effectiveness of interleukin (IL)-12-secreting tumor vaccines in the treatment of mouse tumors could be enhanced by concurrent application of cytokines and costimulatory molecules. We investigated the therapeutic potential of IL-12 gene-transduced melanoma vaccine in combination with CpG immunostimulatory oligodeoxynucleotide (ODN) 1826, an adjuvant known to favor development of Th1-biased immune response, in a B78-H1 (B78) melanoma model in mice. EXPERIMENTAL DESIGN: Mice injected with B78 melanoma cells were treated with irradiated IL-12 gene-transduced B78 cells [B78/IL-12(X)] and/or ODN 1826. Mechanisms responsible for the antitumor effects of the treatment were investigated using fluorescence-activated cell sorter analysis, a standard (51)Cr releasing assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and ELISA. RESULTS: Single injection of B78/IL-12(X) cells had no effect on tumor growth, whereas seven consecutive daily injections of ODN 1826 markedly inhibited tumor progression with occasional curative effects. When used in combination, B78/IL-12(X) cells and ODN 1826 caused additional tumor growth reduction and eradication of tumors in 62% of treated mice. The combined treatment activated local inflammatory response against tumor but also induced systemic antitumor immunity. In vitro studies have shown that when used together, B78/IL-12(X) cells and ODN 1826 induced a potent Th1 response and suggested the role of IFN-gamma in activation of the host immune response. The antitumor effects in double-treated mice were accompanied by the development of cytotoxic effectors in the spleen and activation of macrophages. CONCLUSIONS: The results provided the evidence that the combination of IL-12 gene-modified melanoma vaccine and ODN 1826 induces synergistically systemic and local antitumor immunity.

Animals↗

PubMed2003

Complete tumour regressions induced by vaccination with IL-12 gene-transduced tumour cells in combination with IL-15 in a melanoma model in mice.

In the present study, IL-12 gene-transduced B78-H1 melanoma cells (B78/IL-12) were used in combination with IL-15 to treat melanoma-bearing mice. Genetically modified B78/IL-12 cells, when injected subcutaneously, induced strong activation of antitumour mechanisms resulting in complete loss of tumourigenicity. In a therapeutic model, intratumoural injection of irradiated B78/IL-12 cells significantly delayed tumour growth and led to the regression of melanoma in one case. Similarly, consecutive daily injections of IL-15 markedly inhibited tumour progression with occasional curative effects. When used in combination, vaccination with B78/IL-12 cells and treatment with IL-15 caused eradication of established tumours in all treated mice. The combined treatment with B78/IL-12 cells and IL-15 activated not only a local response against tumour, but also induced systemic antitumour immunity that led to a delay or inhibition of tumour development at a distant site. In vitro studies demonstrated that when used together, B78/IL-12 cells and IL-15 induced a shift from a type Th2 to a type Th1 response. Activation of the antitumour immune response in double-treated mice resulted, in part, from stimulation of IFN-gamma production and was accompanied by the development of cytotoxic effectors in the spleen. As shown in a macrophage tumouricidal assay, macrophages could also play a role in the antitumour effects. The results confirmed that vaccination with IL-12 gene-modified tumour cells is superior to the treatment with unmodified tumour cell vaccine and, additionally, showed that IL-15 is an excellent candidate for adjuvant therapy, inducing synergistically not only a delay of tumour growth but also its complete eradication.

Animals↗

PubMed2003

Gender-related early immune changes in mice exposed to airborne suspended matter.

Immunotoxicity of the airborne suspended matter (ASM) from Upper Silesia (Poland) was investigated. The effect of the mixture of toxic components from the air suspended matter on the distribution and expression of several surface markers on lymphoid cells from thymus, spleen and axillary lymph nodes of female and male mice were examined. Corticosterone, a stress related hormone and sex hormones concentration in the plasma of animals were evaluated to discuss the interplay between the immune and endocrine system. The route, dose and length of application of ASM were examined. Thymus was shown to be a very sensitive organ to the effect of airborne suspended matter. Profound changes were shown in the distribution of CD4+ CD8+, CD4+ and CD8+ thymocytes subsets and TCRbeta and CD3 expression on thymic cells in young mice of both sexes exposed to ASM. Gender-related differences between female and male thymuses are rather quantitative than qualitative. Changes observed in the peripheral lymphoid organs were not so dramatic. The decrease of the percentage of CD19+ and Thy-1.2- in female spleens was noted. None changes in the plasma level of corticosterone and testosterone was observed in mice exposed to ASM, while a profound decrease of estradiol in female mice was noted. An interpretation all of these documented changes is attempted.

Air Pollutants↗

PubMed2002

Cytokines production is altered in mice exposed to airborne suspended matter.

The production of IL-2 and IL-4 by thymocytes, spleen and axillary lymph node lymphocytes from female and male mice exposed to airborne suspended matter (ASM) was the scope of our investigations. Cytokines production by activated lymphocytes was determined by the estimation of the percentage of cells positive for intracellular cytokines and by the concentration of both cytokines secreted into the culture medium. Two models of mice exposure to ASM were used: 1/ intraperitoneal injection (acute exposure), and 2/ oral exposure (subacute model). ASM exposure affected both IL-2 and IL-4 production and IL-2R alpha expression on activated lymphoid cells isolated from different lymphoid organs of both female and male mice. The effect was dependent on the route and duration of exposure, ASM dose and the age and sex of mice. A wide panel of changes is discussed. The prolonged exposure to ASM resulted in overproduction of IL-2 in both female and male mice and in overproduction of IL-4 in male mice. Acute exposure to ASM strongly affected IL-2 and IL-4 production, and the effect varied among lymphocytes from different lymphoid organs. Intracellular cytokines expression and the level of secreted cytokines seem to be good tools for the assessment of toxic effects of environmental pollution on the function of the immune system.

Air Pollution↗