Biomedical subjects

J Michalkiewicz

Publications and source records attributed to J Michalkiewicz.

7 recordsLinked to original sources

PubMed2003

Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis.

BACKGROUND: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. METHODS: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing 'naive' (CD45RA+) and 'memory' (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. RESULTS: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD19+ cells and NK lymphocytes; 2) a reduction in the percentage of 'naive' CD4+ but normal proportion of 'naive' CD8+ as well as CD4+ and CD8+ 'memory' cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of 'naive' and 'memory' T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. CONCLUSIONS: It is concluded that the reduction in number of 'suppressor-inducer-like 'naive' CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.

Adult↗

PubMed1998

Effect of Pseudomonas aeruginosa exotoxin A on CD3-induced human T-cell activation.

The effect of Pseudomonas aeruginosa (PA) exotoxin A (P-ExA) on CD3-induced T-cell activation was studied on the level of T-cells (proliferation, synthesis of interleukin (IL)-2, expression of IL-2R complex, ICAM-1,2 and LFA-1 molecules), and on the level of monocytes (expression of ICAM-1,2, LFA-1 molecules, as well as FcRI and CD14 receptors). We found that: (1) P-ExA blocked T-cell proliferation and this effect was totally reversed by intact monocytes, and partially by IL-2 or TPA but not by costimulatory cytokines (IL-1alpha, IL-1beta, TNF-alpha or IL-6); (2) P-ExA transiently, in short-term cultures (48 h), inhibited synthesis of IL-2; (3) prolonged stimulation (96 h) of peripheral blood mononuclear cells (PBMC) or CD4 + T-cells with P-ExA in high or low doses (100 and 10 ng/ml, respectively), enhanced the level of IL-2 in the cultures; (4) P-ExA at low dose, combined with IL-1beta, TNF-alpha or IL-6, up-regulated synthesis of IL-2; and (5) stimulation of T-cells with anti-CD3 monoclonal antibody (mAb) and P-ExA at high dose diminished the expression of the p55 chain but not of the p75 chain of IL-2R complex and slightly affected the expression of CD3 complex, ICAM-1,2 and LFA-1 molecules. Hence, P-ExA can regulate the level of IL-2 in cultures of CD3-induced T-cells either by inhibition of IL-2 consumption (when P-ExA is applied in high dose), or by induction of IL-2 production (a costimulatory effect exerted by P-ExA in low dose in combination with monokines). Action of P-ExA on monocytes resulted in: (1) inhibition of the expression of ICAM-1,2 molecules and their ligand LFA-1 molecule; (2) low expression of FcRI receptor (a ligand for Fc part of CD3 mAb); and (3) inhibition (over 90%) of the expression of CD14 molecule. In conclusion, P-ExA-induced anergy of T-cells depends on: (a) decrease in the affinity of IL-2R complex on activated T-cells; and (b) inhibition of the accessory activities of monocytes.

ADP Ribose Transferases↗

PubMed1997

Linkage studies exclude the AT-V gene(s) from the translocation breakpoints in an AT-V patient.

An 8-year-old girl with severe microcephaly of prenatal onset, borderline intelligence, defects of skin pigmentation, deficiency of both humoral and cellular immunity, a normal serum alpha-fetoprotein level and hypersensitivity to ionizing irradiation is described. Spontaneous chromosomal breakage in lymphocytes together with the clinical presentation led to the diagnosis of ataxia telangiectasia variant (AT-V). In addition, the patient carried a constitutional translocation of paternal origin: 46,XX,t(3;7)(q12;q31.3) pat. In subsequent linkage and haplotype studies in 12 AT-V families with microsatellite markers from each of the translocation breakpoint regions, we could clearly exclude the localization of an AT-V gene to these regions.

Ataxia Telangiectasia↗

PubMed1991

Activity of B-cell lineage system in the cord blood of newborns.

To evaluate the B cell lineage system in newborns we estimated IL-4 (BCGF/BSF-1) production by lymphocytes isolated from the cord blood and its influence on antibody synthesis. Undertaken experiments were performed in two groups of newborns: stressed newborns mainly with perinatal infection and full-term healthy neonates, comparing to peripheral blood of adults as control. Results revealed 1) the significantly higher percentage of mature B cells (B1) in cord blood of stressed newborns, 2) the significantly higher IL-4 production comparing to full-term neonates, 3) diminished IgG and IgA synthesis in vitro by allogenic activated B cell blasts in the presence of supernatants from cultures of PHA-stimulated lymphocytes isolated from cord blood of stressed newborns. Induction of IgM synthesis by these active supernatants was significantly higher in stressed newborns than in the other examined groups. We suggest that immunoregulatory mechanisms, which control the production of IL-6 (BCDF/BSF-2) are still not completely mature at birth.

B-Lymphocytes↗

PubMed1990

Influence of immune complexes containing HBsAg and HBeAg on IL-2 dependent human lymphocyte proliferation.

Studies were undertaken to evaluate the effect of hepatitis B virus (HBV) immune complexes (HBV-IC) on IL-2 dependent human lymphocyte proliferation. The following parameters were studied: 1) Effect of HBV-IC (HBsAg-IgG or HBeAg-IgG) on PHA-mediated lymphocyte proliferation; 2) Influence of HBV-IC on the ability of PHA-stimulated peripheral blood lymphocytes (PBL) for IL-2 production and IL-2 receptor expression. HBV-IC induced a dose dependent and antigenic dependent suppression of PHA stimulated lymphocytes. The suppressor effect exerted by HBsAg-IgG was irreversible. In contrast, the suppression mediated by HBeAg-IgG was reversible: lymphocytes preincubated with this preparation washed and activated with PHA responded well to mitogen. The presence of HBV-IC in the cultures of PHA-activated PBL decreased their ability to produce IL-2: HBeAg-IgG exerted a stronger suppressor effect. This effect was partially reversible: removal of HBV-IC from the culture by washing and subsequent stimulation of PBL with PHA increased the capacity of lymphocytes to produce IL-2. This was particularly evident with HBeAg-IgG. Decreased activity of IL-2 observed in the cultures, was also partially dependent on the ability of HBV-IC to bind IL-2 present in the culture medium. Experiments performed using ultracentrifugation indicated that HBV-IC, especially HBsAg-IgG, may bind to IL-2 and inactivate it. HBV-IC had also an effect on IL-2 receptor expression: 1) their presence in the cultures of PHA-stimulated PBL decreased the number of Tac positive cells; 2) the response of HTCL to exogenous IL-2 was decreased by HBV-IC present in the culture medium. This was especially observed in the case of HBsAg-IgG. We suggest that the observed inhibition of PHA-induced lymphocyte proliferation exerted by immune complexes containing HBsAg-IgG or HBeAg-IgG may be caused mainly by their influence on IL-2 dependent mechanism of lymphoproliferation.

Antigen-Antibody Complex↗

PubMed1989

Effect of HBV antigens and their immune complexes on the PHA induced lymphocyte proliferation. Modulatory influence on interleukin-2 activity.

Studies were undertaken to evaluate immunomodulating properties of Hepatitis B virus (HBV) preparations: HBsAg, HBeAg and their complexes: HBsAg-IgG and HBeAg-IgG, on PHA-induced lymphocyte proliferation. Cells were obtained from blood of healthy individuals, serologically negative for HBV markers. HBV preparations were purified from sera of children with HBV-mediated glomerulonephritis. Suppression of lymphocyte proliferation observed in the presence of HBsAg and HBsAg-IgG complexes was irreversible. However, the suppressive effect of HBeAg and HBeAg-IgG was abolished when these preparations were removed from the culture. Addition of exogenous interleukin-2/IL-2/reversed only the suppressive effect of HBeAg-IgG which was constantly present in the culture. The inhibition of lymphocyte proliferation correlated well with the decreased level of IL-2 activity in cultures with HBV-preparations. Experiments performed using ultracentrifugation indicated that HBV preparations, especially HBsAg and HBsAg-IgG, may bind to IL-2 and inactivate it in supernatants. The experiments indicate that HBV antigens, as well as other viral products, can inhibit lymphocyte proliferative response to the mitogen. Furthermore, we suggest that this inhibition may occur via suppression of IL-2 synthesis.

Antigen-Antibody Complex↗

PubMed1988

Primary immunodeficiency diseases in children treated in the Children's Memorial Hospital, Poland.

One hundred and three cases of primary immunodeficiency diseases were diagnosed among children suffering mainly from chronic and severe infections in the period 1980-1987. Predominantly antibody defects were recognized in 48 patients (46.6%), combined immunodeficiencies in 36 patients (35%), phagocytic disorders in 12 patients (11.6%), complement defects in 6 patients (5.8%), and cell-mediated disease (Di George syndrome) in 1 patient. Allergic complications were observed in 25 patients (24.2%) and malignancy-in 3 patients (2.9%). More detailed immunological studies were performed in children with X-linked agammaglobulinemia in the course of intravenous immunoglobulin therapy and in children with ataxia telangiectasia.

Child↗