Search PubMed⌕ Search

Biomedical subjects

T Diamantstein

Publications and source records attributed to T Diamantstein.

At least 91 records · Page 5Linked to original sources
PubMed1989

The dipeptide Lys-Pro restores the diminished wound healing following treatment with anti-T-helper cell monoclonal antibody.

To determine the role of T-cell subsets in wound healing, we studied the granulation tissue proliferation after depletion of CD4 or CD8 positive cells. Granulation tissue proliferation in CD8-diminished AB mice was significantly higher than in the control group as a result of depleted suppressor cell activity. The CD4-depleted mice produced granulation tissue in less than 30% of the control group. To investigate the role of dipeptidylpeptidase IV on CD4 positive cells in wound healing we used Lys-[Z(NO2)]-Pro, a chemically modified dipeptide which may result by degradation of polypeptides by this peptidase. It was possible to restore the diminished capability of granulation tissue proliferation in CD4-depleted mice by a single treatment with the dipeptide Lys-[Z(NO2)]-Pro. Our results suggest that: (i) the CD4 positive T-helper subset regulates wound healing, and (ii) products of degradation by dipeptidylpeptidase IV may bypass T-helper cell function.

Animals↗
PubMed1989

Immunotherapy of experimental autoimmune encephalomyelitis (EAE): differential effect of anti-IL-2 receptor antibody therapy on actively induced and T-line mediated EAE of the Lewis rat.

Treatment of Lewis rats with monoclonal anti-interleukin-2 receptor (IL-2 R) antibody ART-18 is highly efficient in protecting the recipients from T-line transferred experimental autoimmune encephalomyelitis (tEAE) in vivo. In contrast, ART-18 did not affect the development of EAE actively induced (aEAE) by immunization with myelin basic protein (MBP) in complete Freund's adjuvant (CFA). ART-18 caused a slight delay in the development of aEAE only in combination with a subtherapeutic dose of cyclosporine A (Cy-A), but failed to influence duration or severity of clinical signs. The discrepancy in therapeutic efficiency of ART-18 in tEAE and aEAE could be due to a different intensity of IL-2 R-expression on in vitro- and in vivo-activated MBP-specific T cells. Our results therefore caution against a general therapeutic application of anti IL-2 R-directed therapy in all manifestations of T-cell-mediated autoimmunity.

Animals↗
PubMed1989

Current stage of interleukin 2 receptor targeted therapy.

The overview summarizes a new and selective form of immunosuppressive therapy by using anti-Interleukin-2 receptor monoclonal antibodies, which may soon become an important form of recipient treatment in organ/tissue transplantation or/and of patient treatment with auto-immune diseases.

Animals↗
PubMed1989

Ciamexone suppressed anti-islet ADCC of mononuclear cells and serum from type 1 (insulin-dependent) diabetic patients.

ADCC (Antibody-dependent cellular cytotoxicity) against xenogenic islets has frequently been found in newly diagnosed Type 1 (insulin-dependent) diabetics suggesting that when combined with autologous serum in vitro, the destruction of islet cells caused by mononuclear cells (MNC) reflects islet destruction in vivo. In this study the ability of Ciamexone to suppress the anti-islet ADCC in vitro was investigated. We selected both ADCC positive and ADCC negative subjects from a group of Type 1 diabetics. The targets, islets from neonatal rats, were incubated for one hour with the probands serum. The ADCC was then measured by the 51Cr-release of the serum-treated islets after a 6h-incubation with MNC of the same donor. Results both with and without co-incubation of Ciamexone were compared. Ciamexone does not influence the spontaneous 51Cr-release from neonatal rat islets treated with the probands serum but significantly suppresses the anti-islet ADCC. The fact that Ciamexone suppresses anti-islet ADCC may explain its possible effectiveness in Type 1 diabetes.

Adjuvants, Immunologic↗
PubMed1989

Agonistic and antagonistic interactions of anti-interleukin 2 receptor monoclonal antibodies in rat recipients of cardiac allografts.

A panel of five mouse mAbs recognizing 4 distinct epitopes (R1-4) of the rat 55kD IL-2R molecule were tested for their influence on acute rejection (8 days) of (LEWxBN)F1 cardiac allografts in LEW hosts. IL-2R1 targeted therapy with ART-18 (IgG1, inhibits IL-2-dependent responses) prolonged graft survival to ca.21 days. IL-2R2 is recognized by ART-65 and ART-75, mAbs that do not inhibit T cell growth. Treatment with ART-65 (IgG1) but not ART-75 (IgG2a) abrogated acute rejection (ca. 16 days and 9 days, respectively). ART-35, an anti-IL-2R3 mAb (IgG1, does not inhibit T cell function) extended graft survival marginally to ca. 12 days. Finally, therapy with OX-39, (anti-R4 IgG1 mAb, inhibits IL-2 binding, but not IL-2-driven growth) was completely ineffectual. Simultaneous targeting of two IL-2R epitopes increased the therapeutic index synergistically (ART-18 [R1] + ART-65 [R2]--60% permanent graft acceptance), additively (ART-75 [R1] + ART-35 [R3]--graft survival ca. 18 days), or did not improve further graft survival at all (ART-18 [R1] + OX-39 [R4]--graft survival ca. 18 days). Thus, the cellular targeting patterns and isotype of mAbs are crucial: (1) targeting at functionally distinct epitopes controls rejection most effectively; (2) IgG1 and IgG2b mAbs are more influential in vivo than IgG2a, data supported by the studies employing the family of ART-18 isotype switch variants. Treatment with anti-IL-2R mAb did not depress Ts activity as tested both in vitro and in vivo. Sparing of putative Ts by mAb is also shown by thymectomy of graft recipients before or during ART-18 therapy, which shortened graft survival to 13-15 days; thymectomy after ART-18 therapy did not influence graft survival. However, infusion of IFN-gamma recreated classic acute rejection within 10 days in otherwise longstanding cardiac allografts in ART-18 treated hosts. Upregulation of MHC class II antigen and IL-2R expression seems to be primarily responsible for this striking biological effect of IFN-gamma in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Factors influencing the response to hepatitis B vaccination of hemodialysis patients.

The response rate and HBsAG antibody concentrations were examined after hepatitis B vaccination in 78 hemodialysis patients aged between 29 and 79 years. The values were related to age, duration of hemodialysis, body weight, creatinine, urea nitrogen, serum concentrations of beta 2-microglobulin and soluble interleukin-2 receptor (IL-2R). Patients with low anti-HBsAG antibody concentrations (10-100 mU/ml) had significantly higher IL-2R serum concentrations than those with high anti-HBsAG antibody concentrations (greater than 3,000 mU/ml; p less than 0.05). Discriminant multivariate analysis (p = 0.032) revealed the influence (62%) of IL-2R on the response rate while other factors were similar in all patient groups. It is concluded that preactivation of T cells with an increased release of IL-2R may contribute to impaired immune response after hepatitis B vaccination.

Adult↗
PubMed1989

Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo.

A rat anti-interleukin-2 receptor (IL-2R) monoclonal antibody (mAb), AMT-13, has been shown to prolong cardiac allograft survival in mice. However, neither the mechanism of its immunosuppressive action, nor its other in vivo effects, have been studied extensively. We investigated the effect of AMT-13 on serum-soluble IL-2R levels by a quantitative ELISA technique. Following administration of multiple doses of AMT-13, sufficient to delay fetal pancreatic graft rejection, a rapid and lasting increase in soluble(s) IL-2R levels of up to 20-fold was observed. Levels returned to normal by Day 9 despite continued AMT-13 administration. A similar though less marked increase was observed following a single injection of AMT-13. Irradiation with 350 rads decreased sIL-2R levels, whilst rat Ig-treated control mice had sIL-2R levels within the normal range. In vivo administration of recombinant IL-2 also increased sIL-2R levels, but the effect was transient and slight. No effect on either the release of sIL-2R or expression of cell surface-associated IL-2 receptors was noted when splenocytes were cultured in the presence of AMT-13. We speculate that the increased concentration of sIL-2R in the serum of AMT-13-treated mice may play a role in the immunosuppressive action of this mAb.

Animals↗
PubMed1989

Demonstration of two distinct forms of released low affinity-type rat IL-2 receptors.

The release of IL-2 binding proteins, derived from the 55,000 MW low affinity IL-2R (L chain), has been observed for virtually all L chain-bearing cells in either humans, the mouse or the rat. Based on the characterization of the released human L chain as a molecule 10,000 MW smaller than the cell surface receptor, either proteolytic cleavage or differential splicing of the L chain encoding mRNA have been suggested as mechanisms underlying the receptor release. Combining affinity labelling of the L chain with [125I]IL-2 and immunoprecipitation with L chain-specific monoclonal antibody (mAb) applied for the detection of soluble rat IL-2R revealed the existence of two classes of soluble receptors, one being of the same size as cell surface-expressed L chain, the other of 40,000 apparent molecular mass. These findings raise the possibility of other mechanisms of receptor release than those discussed for human L chain.

Affinity Labels↗
PubMed1989

The therapeutic efficacy of an anti-IL-2 receptor monoclonal antibody correlates with an increase in serum soluble IL-2 receptor levels.

We tested the capacity of three rat monoclonal antibodies (MoAb), recognizing different epitopes on the L chain of mouse interleukin-2 receptor (IL-2R), to block delayed-type hypersensitivity (DTH) and local graft-versus-host reaction (GVHR). Furthermore, we investigated the effect of IL-2R-targeted immunotherapy on serum soluble IL-2R levels by ELISA technique. Following administration of AMT-13 MoAb, in sufficient amounts to suppress both DTH (60-90% inhibition) and local GVHR (55-70% inhibition), an increase in soluble IL-2R levels up to 12-fold was observed. In contrast, the administration of 7D4 MoAb did not show any immunosuppressive effect in vivo and even decreased the soluble IL-2R levels. The third anti-IL-2R MoAb AMT45-20 had an intermediate effect. AMT45-20 MoAb marginally suppressed the DTH as well as local GVHR (15-35% inhibition) and induced only a slight increase in soluble IL-2R levels (up to 4-fold). Both cyclosporin A, a conventional immunosuppressive drug, and the anti-L3T4 MoAb, which defines the entire T helper cell subset, suppressed GVH and DTH response but did not increase the soluble IL-2R serum levels. The increased concentration of soluble IL-2R in the serum of successfully treated mice may be due to destruction of IL-2R-positive cells by anti-IL-2R-targeted immunotherapy and seems to be a sensitive indicator for the success of such a therapy.

Animals↗
PubMed1988

Immature, double negative (CD4-,CD8-) rat thymocytes do not express IL-2 receptors.

IL-2R alpha-chain is expressed on a subset of mouse CD4- and CD8-, double negative (DN) thymocytes. This expression of IL-2R alpha-chain on some DN thymocytes in the mouse has led to the proposal that IL-2 might serve as a principal growth and/or differentiation factor for immature thymocytes. However, previous histologic observations have indicated that IL-2R alpha-chain is not expressed on the subcapsular thymic blasts (an area rich in DN cells) in either huma or rat thymus, whereas all three species display IL-2R expression on a few cells in the thymic medulla. Therefore, we characterized rat DN thymocytes to determine whether they contained an IL-2R+ population. The results show that rat thymic DN cells share several characteristics with mouse DN cells. However, most of the rat strains do not express the IL-2R on DN cells as shown either by immunofluorescence or by IL-2 binding and receptor cross-linking. Thus, the rare medullary IL-2R+ cells were not found in the DN cells. Only in the exceptional F344 rat strain is the IL-2R alpha-chain expressed on a major proportion of thymocytes, including both DN cells and small cortical-type thymocytes. Furthermore, rat DN cells do not contain detectable IL-2 mRNA or cytoplasmic IL-2 activity, thus supporting the conclusion that it is unlikely that IL-2 and IL-2R serve to maintain the proliferation of rat DN thymocytes in vivo. The possible significance of in vivo expression of IL-2R alpha-chain on immature thymocytes in the mouse and in a single rat strain is discussed.

Aging↗
PubMed1988

Interleukin 2 modifies the bioelectric activity of some neurosecretory nuclei in the rat hypothalamus.

Introduction of 15-30 U of interleukin-2 (IL-2) into the 3rd ventricle of Wistar rats was followed by a marked and significant decrease in neuron discharge frequency in the ventromedial nucleus of hypothalamus and a marked increase in the supraoptic and paraventricular nuclei. The monoclonal antibody ART62 partly blocked these effects. The conventional anti-IL-2 receptor monoclonal antibody ART18 had only a non-significant influence on the effects of IL-2. Since the supraoptic and paraventricular nuclei secrete the antidiuretic hormone, their excitation may offer a partial explanation of the considerable water retention observed during IL-2 therapy against neoplasia.

Action Potentials↗
PubMed1988

Identification of the blue-sensitive cones in the mammalian retina by anti-visual pigment antibody.

Monoclonal antibodies to visual pigments produced in our laboratory were applied to analyze the distribution of color-specific photoreceptor cells in the retina (photoreceptor mosaic). We demonstrated in two ways that the monoclonal antibody OS-2 specifically recognized the blue-sensitive cone cells in the mammalian retina. First, rabbit photoreceptors damaged selectively by intense blue light were recognized by OS-2 antibody. Second, OS-2-positive cones in the ground squirrel were those with thick inner segments, which is known to be characteristic of the blue-sensitive cones. In addition, the OS-2-positive cones in monkeys have a distribution and pattern characteristic of blue-sensitive cones in that species. In several other species (human, rabbit, cow, and pig), the OS-2-positive cones represent an appropriate minority of the population of photoreceptor cells. The visual pigment recognized by the OS-2 antibody had a relative molecular weight of 36,000, as shown by immunoblotting of 3 mammalian species. All other cones were recognized by another monoclonal antibody, COS-1, which is regarded as specific to middle-to-long-wavelength-sensitive photoreceptors.

Animals↗