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Biomedical subjects

W L Olszewski

Publications and source records attributed to W L Olszewski.

At least 109 records · Page 6Linked to original sources

Immune events in skin. II. Inhibition of dendritic (veiled) cells function and traffic with anti-lymph dendritic cell sera.

The migrating dendritic cells (DC) from the canine skin-draining afferent lymph are the most potent stimulators of the allogeneic MLR of all other lymph cell subpopulations. The MLR could be inhibited by addition of xenogeneic (rabbit), polyclonal anti-lymph dendritic cell serum (ADCS) to the cultures. ADCS blocked the presentation of Ia and CD1 antigens on the surface of DC. Studies using mouse anti-human monoclonal antibodies, cross-reactive with canine cells, indicate that blocking of Ia, but not of CD1 antigen, is responsible for inhibition of MLR. ADCS abrogated also the accessory function of DC in the lymph lymphocytes response to PHA. The inhibition reached 73%, when the serum was added for the whole period of the culture, and 23% after preincubation of DC with ADCS (anti-dendritic cell serum). ADCS administered subcutaneously into the dorsal area of hind paws caused a selective, transient disappearance of DC from the afferent lymph of normal dogs, which lasted for 2 h after the injection. We conclude, that the functional and physical elimination of migrating skin DC mediated by ADCS in vitro and in vivo, justify the possible use of this serum in the combined immunotherapy directed at the prolongation of skin graft survival.

Animals↗

Donor-specific transfusion does not mitigate but accelerates rejection of intravenously transplanted lymphocytes.

Rat allogeneic heart or kidney grafts are rejected within 6 to 8 days, whereas lymphoid cells from the same donor transplanted intravenously across the MHC barrier are eliminated, in most part, within 6 h. We have found that donor specific transfusions (DST) significantly prolonged the survival time of organ allograft but accelerated destruction of i.v. transplanted lymphocytes. Partial elimination of transplanted lymphocytes was observed after third-party blood transfusion. Blocking of the MHC class I and II determinants on transplanted lymphocytes with monoclonal antibodies OX18 and OX6 did not have effect on the lymphocyte elimination kinetics. The effect of hyperacute elimination of allogeneic lymphocytes by DST-treated rats could be adoptively transferred with their sera, although the cytotoxic antibody titer against donor MHC antigens was in these sera low or hardly detectable. DST-recipient sera contained donor-specific IgG and IgM alloantibodies. It seems that these "enhancing" antibodies could block the MHC products on organ graft endothelial cells, thereby preventing attack of circulating donor-specific cytotoxic lymphocytes. At the same time they may opsonize the transplanted lymphocytes, thereby facilitating their recognition and removal in the lymphoid organs of graft recipient.

Animals↗

Skin changes in filarial and non-filarial lymphoedema of the lower extremities.

The pathogenesis of lymphoedema in patients infected with Wuchereria bancrofti or Brugia malayi remains unclear. Lymph stasis and local immunological reactions seem to play the main role. In order to discriminate between the obstructive and immunological effects of the parasite, a comparative histological study of skin specimens obtained from two groups of patients, one with filarial and the other with postsurgical lymphedema of lower extremities, was performed. In both groups patients suffered lymph stasis, in the first due to filariasis, in the other due to removal or irradiation of pelvic lymph nodes. The patients with filarial infection showed hyperproliferation of keratinocytes, focal acantholysis, accumulation of lymphocytes at the epidermo-dermal junction, profuse pericapillary and perivenular mononuclear infiltrations in the dermis marginated granulocytes in capillaries and, in some cases, subepidermal granulocytic infiltrates. There were many dilated initial lymphatics and lymphatic "lakes" between thick collagen fibre bundles. Monoclonal antibody analysis revealed that the most common cells in the infiltrates were macrophages (CD68+). All mononuclear and endothelial cells were HLA-DR+. In contrast, the skin specimens of non-filarial patients revealed only moderate proliferation of keratinocytes, increased numbers of CD1+ epidermal Langerhans cells, moderate pericapillary infiltrates of CD68+, CD4+ and CD8+ cells, and evidently less intensive marking of cells with anti-HLA-DR antibody. There were few initial lymphatics visible. These findings indicate that filarial lymphoedema is complicated by a severe inflammatory component, which is much less expressed in postsurgical lymph stasis.

Adult↗

Immune events in skin. I. Spontaneous cluster formation of dendritic (veiled) cells and lymphocytes from skin lymph.

To investigate the mechanism of spontaneous attachment of afferent lymph lymphocytes to dendritic cells, cells from canine skin lymph were used. There were 3.3 +/- 2.8% of veiled cells in clusters found in lymph flowing from the cannulated lymph vessel. The number of clusters forming ex vivo in the collected lymph samples increased as a function of time and was temperature dependent. Incubation of cells with proteolytic enzymes or monosaccharides did not alter cell interactions. The ability of veiled cells to bind lymphocytes was independent of divalent cations but reduced by xylocaine and retinoic acid. Among steroids only methylprednisolone showed an inhibitory effect on cluster formation. Indomethacin and acetylsalicylic acid had no blocking activity on cell binding. Also, no effect was seen after treatment with cyclosporine A and azathioprine. An enhanced cluster formation after desialation with neuraminidase was observed. The desialated cells were cultured in order to study their stimulatory and accessory cell functions. No enhancement of autologous mixed leucocyte reaction was seen, but a significantly higher responsiveness to a suboptimal dose of phytohaemagglutinin was observed. The N-ase-mediated non-specific cell attachment could be abrogated by cell washing or treatment with EDTA or xylocaine. This study indicates that cluster formation by skin lymph veiled cells and lymphocytes is a spontaneous process which cannot be controlled by means usually effective in regulating the in vitro induced clustering of antigen-stimulated cells.

Animals↗

Immune proteins in peripheral tissue fluid-lymph in patients with filarial lymphedema of the lower limbs.

Immune proteins and cytokine concentrations and activity were measured in skin tissue fluid-lymph and blood serum of patients with lower leg filarial lymphedema. High levels of lymph gamma-globulins, alpha-1-acid glycoprotein and IgG lymph/serum ratio were found. Lymph from filarial patients had an elevated lymph stimulatory effect on blood mononuclear cell culture with phytohemagglutinin. There was also a high concentration and activity of IL-1 beta but gamma-interferon was not detected. The deranged pattern of immune proteins and high activity of IL-1 suggest persistence of an ongoing local inflammatory process despite the absence of overt dermatitis. The high tissue-lymph IL-1 concentration and activity may signify a cytokine network promoting keratinocyte and fibroblast proliferation commonly seen on skin histology in patients with filariasis.

Adolescent↗

Development of antiserum against veiled (dendritic) cells of canine afferent lymph: implications for transplantation biology.

A method is described for production of anti-veiled cell serum against veiled cells (VC) or dendritic cells obtained from canine skin lymph. By use of discontinuous Percoll gradient, VC from lymph were enriched to about 50% of the entire lymph cell population. After immunization of rabbits with the priming total dose of 10(7) VC (intramuscular, subcutaneous, intracutaneous) and with the same total booster injection (intravenous), the sera obtained were cytotoxic mainly for VC, with cytotoxin titer 1:16-1:32 and for agglutinin 1:256-1:512, respectively. Antisera used in vitro blocked the Ia and CD1 antigens of VC on smears and inhibited the accessory function of VC in cell response to phytohemagglutinin (PHA) and their stimulatory activity in mixed leukocyte reaction (MLR). In vivo, the local, intracutaneous administration of antisera led to transient depletion of VC from afferent lymph, and to reduction of mononuclear cells in the T-dependent areas in regional lymph nodes.

Animals↗

Spontaneous cluster formation of dendritic (veiled) cells and lymphocytes from skin lymph obtained from dogs with chronic lymphedema.

To examine the mechanism of spontaneous attachment of afferent lymph lymphocytes to dendritic cells (veiled), we sampled and tested cells from skin lymph in 3 dogs with chronic lymphedema. There were 3.3 +/- 2.8% veiled cells in clusters with lymphocytes in lymph obtained directly from dilated dermal lymphatics by percutaneous puncture. The number of ex vivo clusters forming in the collected lymph samples increased as a function of time and was temperature dependent. The ability of veiled cells to bind lymphocytes was independent of divalent cations but reduced by xylocaine and retinoic acid. Among various steroids tested only methylprednisolone showed an inhibitory effect on cluster formation. Indomethacin and acetylsalicylic acid had no blocking activity on cell binding. Moreover, no effect was seen by cyclosporin A and azathioprine. However, FK 506 had a potent inhibitory effect on spontaneous cluster formation. This study suggests that cluster formation by skin lymph veiled cells and lymphocytes is a spontaneous process which can be controlled in vitro.

Animals↗

Liver sinusoidal cytotoxic cells are recruited from blood and divide locally.

Liver sinusoids contain marginated mononuclear cells which are highly cytotoxic against several tumor cell lines. These cells may play an important role in the elimination of tumor and viral antigens of enteric origin. The question arises whether they are bloodborne, temporarily resident, replacable or permanently resident cells. In order to obtain the answer, a cytogenetic analysis of sex chromosomes in the mononuclear cells from a liver sinusoidal washout of male Lewis rats who had received liver transplants from syngeneic female donors was performed 4 weeks after grafting. About 9% of the liver sinusoidal mononuclear cells obtained from both control and transplanted livers showed mitotic activity, whereas no dividing cells could be found in peripheral blood. In all experiments karyotypic studies of these dividing liver sinusoidal mononuclears from female livers transplanted to syngeneic males revealed in all experiments the male (XY) karyotype. This finding indicates that the cells under study were of blood origin and are not a constitutive cellular component of the liver. They are probably recruited by the liver and divide locally at a signal of a so far unknown origin.

Animals↗

The effect of moderate operative trauma on the blood lymphocyte reactivity--immunomodulatory effect of interleukin-2.

The influence of moderate operative trauma on lymphocyte responsiveness to phytohemagglutin (PHA) and in autologous mixed lymphocyte response (AMLR) was studied. Furthermore, production of interleukin 2 (IL2) and immunomodulatory effect of exogenous IL2 on lymphocyte reactivity after surgery were examined. The responsiveness to PHA declined on day 1 (p less than 0.05) and the level of AMLR was found decreased on days 1 (p less than 0.05), 3 (p less than 0.02) and 5 (p less than 0.03) after surgery. Production of IL2 significantly decreased on day 1, 3 and 5 (p less than 0.05) after operation. Supplementation of PHA and AMLR cultures with exogenous IL2 restored the attenuated postoperative responsiveness to the levels observed preoperatively. This observation may justify IL2 therapy in surgical patients with high risk of uncontrollable postoperative infections.

Adjuvants, Immunologic↗

Immunophenotypic and functional characterization of peripheral blood mononuclear cell populations in patients with dilated cardiomyopathy.

Cell-mediated immune responsiveness was evaluated in 8 patients with dilated cardiomyopathy (CDM). The percentage of blood OKM1 (monocytes), OKT3 (T-cells), OKT4 (helper cells), OKT8 (suppressor cells) and Leu7 (NK) positive cells remained within the normal range whereas the percentage of Leu11 (NK) and OKIa1 (Ia determinant) positive cells was found to be decreased. The natural killer (NK) cell cytotoxicity was significantly lowered. The ConA-suppressor cell activity was seen to be enhanced while the responsiveness of lymphocytes to ConA was diminished. Thus, no consistent numerical changes in lymphocyte subsets were observed in patients with CDM. Some functional deficiencies were, however, detected, and it is possible that these may play a role in the pathogenesis of CDM.

Adult↗

[Allogeneic lymphocytic cytotoxicity].

Allogeneic lymphocyte cytotoxicity (ALC) is identified in vivo by injecting radiolabeled lymphocytes into syngeneic and allogeneic animals and comparing the distribution of radioactivity in several body compartments, usually 6 hr after injection in both types of host. Destruction of the labeled cells in allogeneic recipients is associated with the reduction in radioactivity recovered from the lymph nodes and lungs and increase in the radioactivity in plasma, kidney and urine. The mechanism of the ALC is reviewed.

Animals↗