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L M Vaessen

Publications and source records attributed to L M Vaessen.

87 records · Page 5Linked to original sources

T-cell development during ageing in congenitally athymic (nude) rats.

We studied the thymus-dependent immune system in congenitally athymic (nude) rats of the WAG (RT-1u) strain, at the ages of 2, 3, 5, 9, and 17 months. This included the histology of spleen, lymph nodes, and Peyer's patches, immunohistochemistry on tissue sections, and immunocytology on cell suspensions using a panel of monoclonal antibodies to T-lymphocyte subpopulations, in vitro mitogen responsiveness, and in vivo responsiveness to ovalbumin immunization. The results were compared with those in euthymic immunocompetent littermates of the same age. The cell marker analysis, especially in nude animals, was hampered by the staining of non-T cells by some of the antibodies (staining of putative macrophages, natural killer cells, cells of B-lymphocyte lineage, and of myeloid lineage). Despite this, with age an increase in cells with these markers was observed; for instance, in spleen suspensions, cells labelled by the pan-T reagent MRC OX-19 increased from 5% at 2 months to 19% at 17 months (value in euthymic animals 34%). In the other assays too a gradual increase of T-cell reactivity with age was observed, from almost absent in 2- and 3-month-old nude rats to values in 17-month-old animals of about half the level found in euthymic rats. However, none of the nude animals responded to ovalbumin immunization. These results indicate that in nude animals processes occur which compensate for the absent intrathymic T-cell generation. This applies in particular to changes in T-cell phenotype and mitogen responsiveness, but not to antigen responsiveness.

Aging↗

The effect of melatonin and other indole derivatives in maintaining ovulation in rats kept in continuous light and the influence of these indoles on HIOMT activity in the pineal gland.

The aim of the present study was to investigate whether the ovulation-maintaining effect of melatonin in rats, exposed to continuous light (LL), was also exerted by other pineal indoles which have been reported to influence the reproductive processes of mammals. The effect of 10 micrograms melatonin was compared with that of similar amounts of either N-acetylserotonin, 5-methoxytryptophol, 5-methoxyindole-3-acetic acid, 5-hydroxytryptophol, 5-methoxytryptamine or 5-methoxytryptophan. All these compounds appeared to be significantly less effective than melatonin in preventing the effect of LL, ovulation being preserved in only 20--33% of the rats investigated, with melatonin this percentage being 60--75%. Investigations were also carried out to assess the effect of these indole derivatives on HIOMT (hydroxyindole-O-methyl transferase) activity in synthesizing different 5-methoxyindoles in the abnormally influenced pineal gland due to LL. Melatonin, the compound the effect of which on ovarian cyclicity is strongest, stimulates 5-methoxytryptophol synthesis; while other less active compounds stimulate the synthesis of melatonin and inhibit that of O-acetyl-5-methoxytryptophol. The possibility that the effect of other indoles than melatonin on ovarian cyclicity might be due to stimulation of melatonin synthesis was considered. A possible functional relationship of the different indoles cannot be excluded.

Acetylserotonin O-Methyltransferase↗

Intragraft monitoring of rejection after prophylactic treatment with monoclonal anti-interleukin-2 receptor antibody (BT563) in heart transplant recipients.

BACKGROUND: Anti-interleukin-2 receptor monoclonal antibodies have been used successfully in the prevention of rejection in cardiac allografts in several animal models. METHODS: In an open randomized study murine monoclonal CD3 antibody and BT563, a murine anti-interleukin-2 receptor monoclonal antibody, were given as rejection prophylaxis during the first week after heart transplantation. Cyclosporine therapy was initiated at the third postoperative day. RESULTS: In half the BT563-treated patients an early rejection was histologically shown at week 1, whereas heart transplant recipients treated with murine monoclonal CD3 antibody had a rejection incidence at week 1 of only 9%. During BT563 treatment CD25-positive cells (i.e., cells bearing the interleukin-2 receptor) were not detectable in peripheral blood. However, immunohistologic studies of endomyocardial biopsy specimens taken 1 week after transplantation showed the presence of CD25-positive cells within these specimens in 8 of 10 (80%) of patients with rejection. In patients without rejection CD25-positive cells were present in the biopsy specimens of only two of nine patients (22%). Reverse-transcriptase polymerase chain reaction studies on biopsy material showed the presence of messenger RNA for the interleukin-2 receptor in all and for interleukin-2 in three of five (60%) of biopsy specimens of rejecting grafts. CONCLUSIONS: Although CD25-positive cells were not detectable in peripheral blood during BT563 treatment, these cells were at the same time found to be present within 80% of the endomyocardial biopsy specimens from the rejecting grafts. By initiating cyclosporine treatment at day 0, the synergistic effect of combining cyclosporine and anti-interleukin-2 receptor monoclonal antibodies may result in a lower rejection incidence.

Animals↗

Different patterns in donor-specific production of T-helper 1 and 2 cytokines by cells infiltrating the rejecting cardiac allograft.

BACKGROUND: Cytokines play an important role in allograft rejection. The local production of cytokines by T-helper 2 cells within an allograft could influence the induction of graft rejection. METHODS: Therefore we studied the in vitro production of cytokines by cells infiltrating the graft. graft-infiltrating cell cultures derived from human endomyocardial biopsy specimens more often produced interleukin-2 (p < 0.001), interferon-gamma (p < 0.001), interleukin-4 (p = 0.02), and interleukin-6 (p = 0.04) after stimulation with a B-cell line obtained from the heart donor than after stimulation with a third-party B-cell line. Furthermore, the levels of these cytokines were significantly higher after donor stimulation than after third-party stimulation (p < 0.001). RESULTS: Within the first 90 days after heart transplantation, significantly higher levels of interleukin-2 (p = 0.050 and interferon-gamma (p = 0.02) were produced by donor-stimulated lymphocyte cultures derived from biopsy specimens taken during a rejection episode compared with cultures from biopsy specimens taken during a period without rejection. After 90 days, the levels of T-helper 1 cytokine (interleukin-2 and interferon-gamma) production were, irrespective of the rejection grade, comparable with those found in the cultures from rejection biopsy specimens taken early after transplantation. With regard to T-helper 2 cytokines (interleukin-4 and interleukin-6), no relation was found with the presence of rejection at any time after transplantation. CONCLUSIONS: These data suggest that in the first 3 months after heart transplantation, acute rejection is associated with the production of increased levels of T-helper 1 cytokines but not of T-helper 1 cytokines but not of T-helper 2 cytokines by donor stimulated graft-infiltrating lymphocytes. Thereafter, the T-helper 1 cytokine production of graft-infiltrating lymphocytes remained high, suggesting a continuous state of immunologic activity even in the absence of rejection.

B-Lymphocytes↗