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A Mirisklavos

Publications and source records attributed to A Mirisklavos.

13 recordsLinked to original sources
PubMed1990

T suppressor cells induced by transfusions and cyclosporine. Studies in the murine cardiac allograft model.

Pregraft transfusion combined with immunosuppression at the time of grafting improves the survival of clinical and experimental allografts. The mechanisms responsible for this effect were investigated in the murine model of cardiac transplantation, combining transfusions 7 to 30 days prior to transplantation with cyclosporine 100 mg/kg, 7 to 20 days pregraft or on days 0, 4, and 6 after grafting. Pregraft DST, third-party blood, and CsA all improved graft survival in the BALB/c-to-CBA donor-recipient combination. In animals treated with DST at 14 days pregrafting, 4/9 grafts survived for greater than 100 days. In those given C57BL/6 blood, or CsA on days 0, 4, 6 postgraft, 1/9 grafts survived for greater than 100 days. When 10(7) spleen cells from DST-treated CBA mice with long-surviving BALB/c heart grafts were transferred to naive CBA mice that then received a BALB/c heart 24 hr later, the transferred cells prolonged graft survival, with all grafts functioning at greater than 40 days, and 4/7 at greater than 100 days. Selective removal of T cells from the spleen cell population prior to transfer showed that L3T4+ T cells, but not Ly-2+ T cells, were required to maintain BALB/c allografts. Combining a short course of CsA with DST was more effective than either treatment alone. The most effective combined treatment was DST at day -14 with 100 mg/kg CsA given on days 0, 4, and 6 postgrafting (8/10 grafts survived greater than 100 days). This treatment also induced splenic suppressor T cells of the L3T4+ Ly-2- phenotype. These results clearly show that L3T4+ splenic T suppressor cells are induced by donor-specific blood transfusion with or without CsA treatment, and that these cells play a role in maintaining long-term tolerance to allografts in the mouse heart transplant model.

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PubMed1988

Electrocardiographic monitoring of cardiac transplants in mice.

In the murine cardiac model for vascularised transplantation graft function may be monitored by direct palpation, electrocardiography, and graft histology. To assess the merits of these methods, and to measure ischaemic damage, isografts and allografts were examined at regular intervals from 0 to 60 days after grafting. Heart transplants were vascularised from the abdominal great vessels, using microsurgical techniques, with ischaemic times of less than 60 min. Isografts showed no decrease in heart rate over 60 days, as measured by palpation and electrocardiography, but the voltage of the ventricular complex fell progressively over the first 28 days after grafting then remained stable for more than 60 days. The voltage drop was associated with atrophy of myocardial tissue. Allografts in recipients treated with rabbit antimouse antilymphocyte serum were maintained for more than 60 days with little change in palpation rate or recorded heart rate but with significant falls in ventricular complex voltage, reflecting myocardial atrophy and fibrosis. Untreated allografts were rejected in 10-14 days and showed a rapid fall in palpated heart rate, measured heart rate, and ventricular complex voltage. Thus, in this study, palpation of the heart graft gave an accurate measure of the pulse rate and correlated with electrical activity in acutely rejecting grafts, but in long surviving grafts measurement of ventricular complex voltage showed myocardial damage that was not detectable by direct palpation.

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PubMed1987

The effect of operative ischemia in murine cardiac transplantation: isograft control studies.

Isograft studies were performed in the murine model of cardiac transplantation to investigate the morphologic effects of operative ischemia. Primarily vascularized CBA mouse hearts were grafted heterotopically into the recipient CBA mouse's abdomen with standard microsurgical techniques. After ischemia times of 30 and 60 minutes, histologic examination showed minimal myocardial damage, with necrosis or scarring occupying less than 5% of the cross-sectional area of hearts bisected from apex to base after grafts had been removed on the seventh day after transplantation. Maximal ischemic damage was seen at 7 days after transplantation after 120 minutes of ischemia, with more than 30% myocardial necrosis or scarring of myocardial tissue. Isografts performed with ischemia times of less than 60 minutes were followed for more than 100 days. All hearts showed a fine, generalized, perimyocytic fibrosis, which was maximal at 28 days after transplantation and did not progress thereafter. These results will serve as important control measures for future studies in this model because ischemic damage must be considered in examining histologic samples from long-surviving cardiac allografts maintained in immunosuppressed recipients.

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PubMed1986

Characterisation of cyclosporine-induced suppressor cells in murine delayed-type hypersensitivity responses.

The effect of Cyclosporine A (CsA) on T cell-mediated delayed-type hypersensitivity (DTH) reactions to murine alloantigens was analysed by transferring spleen cells from sensitised and suppressed mice into irradiated naive recipients. Selective removal of Thy1+, Ly1+ or Ly2+ cells prior to intravenous transfer of cells from alloantigen-sensitised mice showed that Ly1+ Thy1+ cells transferred sensitivity. Concomitant treatment of mice with alloantigen and CsA suppressed the DTH response to alloantigens, and spleen cells transferred from these suppressed mice abrogated the response of sensitised cells transferred at the same time. The suppressor cells were strain-restricted and antigen-specific with the surface phenotype Thy1+, Ly1-Ly2+.

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PubMed1986

Effects of cyclosporin A, antilymphocyte serum and donor-specific transfusions on murine delayed-type hypersensitivity and skin graft survival.

The effect of immunosuppressive reagents cyclosporin A (CsA) and rabbit anti-mouse antilymphocyte serum (ALS) on the response to alloantigens was studied in inbred mouse strains. Alloantigen was given either as a cell suspension which induced a delayed-type hypersensitivity reaction (DTH), or as a full-thickness skin graft. Dose-response studies showed that DTH reactions in CBA mice sensitised to BALB/c cells were reduced to background levels when recipient mice were treated with 100 mg/kg CsA on days 0, 4 and 6 after primary alloantigenic challenge. The response to a second challenge was significantly decreased by CsA treatment during primary or secondary exposure to alloantigen and CsA was as effective as ALS in abrogating both primary and secondary DTH reactions. Survival of full-thickness grafts of BALB/c skin on CBA mice was increased from 9 to 23 days by ALS treatment on days -1 and +2, with grafts given on day 0. Long-term treatment with CsA, from day -14 to +12, also prolonged graft survival from 9 to 18 days but donor-specific transfusions, with or without concomitant ALS or CsA treatment, decreased graft survival and often sensitised the recipients. This occurred with transfusions administered from -63 to -7 days and on the day of grafting. Thus, in H-2 mismatched mice, both CsA and ALS treatments produced a state of tolerance when administered during short-term exposure to alloantigen.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

A single dose of UV radiation suppresses delayed type hypersensitivity responses to alloantigens and prolongs heart allograft survival in mice.

The systemic effect of ultraviolet (UV) irradiation on delayed type hypersensitivity (DTH), contact hypersensitivity (CHS) and allograft rejection was investigated in BALB/c mice which had been exposed to a single 1 h treatment with UV radiation (27 kJ/m2) from FS40 sunlamps (60% UVB). After UV irradiation (3-5 days), mice were treated on an unirradiated site with either a subcutaneous injection of allogeneic spleen cells or a topical application of the contact sensitizer oxazolone (OX). The DTH response to allogeneic cells and the CHS response to OX elicited 6 days after immunization were significantly lower in UV-treated mice than in normal mice. Spleen cells from these animals were transferred intravenously into X-irradiated (600R) recipients which were immediately challenged with antigen and the DTH or CHS response elicited was determined 24 h later. Recipients of equal numbers of cells from sensitized and normal animals (6 X 10(6) from each donor) exhibited positive DTH or CHS responses to the antigen used to sensitize the donor. In contrast, recipients of equal numbers of cells from animals sensitized and UV suppressed to the same antigen showed a suppressed DTH or CHS response. This suppression was antigen-specific. Treatment of cells from UV suppressed animals, prior to transfer, with complement and cytotoxic anti-Lyt 2 or anti-Thy 1.2 monoclonal antibodies abrogated the suppressive ability of these cells, in contrast to cytotoxic treatment with anti-L3T4 or anti-Lyt 1 monoclonal antibodies which had no significant effect. The suppressor cells therefore had the phenotype Thy 1.2+, Lyt 2+, L3T4-, Lyt 1-.(ABSTRACT TRUNCATED AT 250 WORDS)

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