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F H Claas

Publications and source records attributed to F H Claas.

At least 73 records · Page 4Linked to original sources
PubMed1998

The frequency and avidity of committed cytotoxic T lymphocytes (cCTL) for donor HLA class I and class II antigens and their relation with graft vascular disease.

Cellular immune processes may trigger the development of graft vascular disease (GVD). CD4 and CD8 cytotoxic T lymphocytes that infiltrate the allograft could play a role in the development of GVD. We studied the presence of in vivo primed or committed CTL (cCTL) and their avidity for donor HLA class I and class II antigens in graft-infiltrating lymphocyte cultures propagated from endomyocardial biopsies derived from patients with and without signs of GVD. The fraction of cCTL with high avidity for HLA class I or class II antigens was estimated by the addition of anti-CD8 or anti-CD4 MoAbs to the cytotoxic phase of the limiting dilution analysis. In the first year after transplantation no difference in the frequency of donor-specific class I cCTL between patients with and without GVD was found. Addition of anti-CD8 MoAb revealed that most cultures predominantly consisted of cCTL with low avidity for donor HLA class I antigens, irrespective of the development of GVD at 1 year after transplantation. However, in patients who did not develop GVD, the frequency of cCTL with donor HLA class II specificity was significantly higher than in patients who did develop GVD. The avidity for donor HLA class II antigens was comparable in both groups. A high frequency of donor-specific cCTL for HLA class II antigens seems to be a protective factor against the development of GVD. These cCTL might be cytotoxic for cells involved in GVD development, e.g. activated endothelium and smooth muscle cells of donor origin.

Antibodies, Monoclonal↗
PubMed1998

HLA class I phenotype and genotype alterations in cervical carcinomas and derivative cell lines.

Downregulation of HLA class I expression is a common event in tumor biology. Various underlying mechanisms have been defined in different tumors, but the knowledge of HLA loss mechanisms in cervical carcinoma is limited. To identify causalities for loss of surface expression, we performed a detailed investigation of HLA class I phenotypes and genotypes in 5 primary cervical tumors and on derivative cell lines. Protein expression on primary tissues and cell lines was evaluated by immunohistochemistry and flow cytometry respectively, using a broad panel of allele-specific monoclonal antibodies. Loss of expression was seen in 3 cases, comprising B15-locus loss, B15-allelic loss, and loss of an A74/B15 haplotype and an A24 allele of the other haplotype. Cytokine treatment induced re-expression of the B15-locus loss, suggesting a regulatory defect underlying lack of constitutive expression in this tumor. In contrast, molecular analyses at the DNA and/or RNA level showed that the other, non-inducible, losses were associated with chromosomal HLA gene defects. Loss of heterozygosity analysis was performed to confirm larger genomic deletions. This study shows that HLA gene defects by mutation or loss of heterozygosity as well as regulatory defects are involved in cervical carcinogenesis. The resulting changes in HLA expression may directly affect the efficacy of the immune response to these human papillomavirus-related neoplasms. Heterogeneity in the underlying loss mechanisms may offer individual tumors various opportunities to escape immune surveillance, and may severely compromise T-cell based therapy.

Alleles↗
PubMed1998

Expression of HLA class I antigens in transporter associated with antigen processing (TAP)-deficient mutant cell lines.

Cells lacking expression of the transporter associated with antigen processing (TAP) are deficient in surface HLA class I, yet express reduced levels of HLA-A2 antigen through TAP-independent processing pathways. We have analysed the expression of HLA-A, -B and -C antigens on the 721.174 and T2 TAP-deficient mutant cell lines using a panel of monoclonal antibodies specific for the HLA antigens encoded by the genotype of these cells. Our study has shown the constitutive expression of HLA-Cw1 molecules on the cell surface of both T2 and 721.174 cells and has confirmed that HLA-A2 and HLA-B51 are expressed at low levels. Transfection of 721.174 cells with cDNAs encoding TAP1 and TAP2 proteins did not fully restore HLA class I antigen expression on these cells, which appeared to be mainly due to a deficiency in expression of the HLA-B51-associated Bw4 epitope. This suggests that additional antigen-processing genes may be required for optimal generation of HLA-B-binding peptides. Our results indicate that TAP-independent pathways of antigen-processing provide peptides for functional expression of all three classical HLA class I molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

A human monoclonal antibody against HLA-Cw1 and a human monoclonal antibody against an HLA-A locus determinant derived from a single uniparous female.

Two human monoclonal antibodies (HuMAbs) with widely different HLA specificities were raised from a uniparous HLA-seropositive female. Screening against a large panel of serologically HLA-typed lymphocytes in the complement-dependent cytotoxicity test showed that one of these HuMAbs, VP6G3, was specific for HLA-Cw1, thereby constituting the first HuMAb against an HLA-C locus product. The second HuMAb, VP5G3, was directed against an HLA-A-encoded determinant shared by HLA-A11, -A25, -A26 and -A66. The epitopes responsible for binding were determined by comparing the aminoacid sequences and were pinpointed to the 6K/9F combination for HuMAb VP6G3, and 163R with a critical contribution of aminoacids present at positions 166/167 for HuMAb VP5G3.

Animals↗
PubMed1998

The impact of special programs for kidney transplantation of highly sensitized patients in Eurotransplant.

Highly immunized patients will continue to accumulate on the waiting list of many registries unless special allocation programs are introduced. In Eurotransplant such patients can benefit from 2 programs, the Acceptable Mismatch (AM) and the Highly Immunized Tray (HIT) programs. Kidney exchange is mandatory in these programs. In addition, highly immunized patients who do not participate in these programs profit from additional points in the allocation procedure (ET-HI). In the past 18 months the 3 programs have run in parallel. Here, we show that the AM and HIT programs are highly effective with respect to increasing the patient's chance of finding a crossmatch negative donor in an adequate time course. Furthermore, the transplantation results of AM and HIT are at least comparable to those of the ET-HI. The main gain at present seems to be the significantly shorter waiting time in the AM and HIT programs.

Europe↗
PubMed1997

Modulation of the T cell compartment by blood transfusion. Effect on cytotoxic and helper T lymphocyte precursor frequencies and T cell receptor Vbeta usage.

Recent data suggest that the favorable effect of pretransplant blood transfusion (BT) on transplant outcome depends on the HLA match. HLA-DR or haplotype shared transfusions lead to transplantation tolerance, and HLA-mismatched BT leads to immunization. The immunological mechanism involved is still unknown. To investigate the effect of HLA compatibility between blood donor and recipient on the T cell compartment, we determined the frequency of cytotoxic and helper T cell precursors specific for blood donor cells (n=20) and the T cell receptor Vbeta (TCRBV) repertoire of the CD4- and CD8-positive peripheral blood mononuclear cells before, at 2 weeks after, and at more than 10 weeks after BT (n=10). Patients had received one transfusion of a nonstored (<24 hr after withdrawal) erythrocyte concentrate without buffy coat containing on average 6x10(8) leukocytes. Eight patients shared an HLA-B and -DR antigen, nine patients shared one HLA-DR antigen, and three patients shared no HLA class II antigens with the blood donor. All patients showed a significant increase in both cytotoxic and helper T cell precursor frequencies against the blood donor 2 weeks after BT. In most patients, the frequencies reached pretransfusion levels again long after BT. In 5 of 10 patients, an expansion of one or more TCRBV families was observed in either the CD4 or CD8 compartment. This study demonstrates that BT, irrespective of the degree of HLA matching, induces activation of the T cell compartment. The degree of sharing of HLA antigens was not correlated with quantitative changes in cytotoxic T lymphocyte precursor or helper T lymphocyte precursor frequencies, or changes induced in the TCRBV repertoire. Cytotoxic and helper T lymphocyte precursor frequencies and TCRBV repertoire determined after BT do not give an indication for a state of tolerance prior to transplantation.

Blood Donors↗
PubMed1997

Transplant rejection associated with the presence of human leucocyte antigen antibodies detected by the Fc gamma R inhibition test but not by the lymphocytotoxicity test.

The unselected sera from 869 human leucocyte antigen (HLA) immunized patients awaiting a kidney transplant were analysed using the complement-dependent lymphocytotoxicity test (LCT) with peripheral mononuclear blood cells and the complement-independent immune phagocytosis inhibition test (IPI) with monocytes derived from between five and 10 donors. Sera from 659 patients were LCT and IPI negative when tested against this small panel. Seventy-nine patients had HLA immunoglobulin-G (IgG) antibodies, detectable by the IPI only. Sera from 117 patients had concordantly positive IPI and LCT reactivity with cells from certain donors and concordantly negative IPI and LCT reactivity with cells from other donors (no isolated IPI and no isolated LCT reactions). Fourteen patients had a mixed type of reactivity. Laboratory findings were interpreted along with the transplantation history of the respective patients. Group 1 comprised patients for whom negative results were obtained in both the LCT and the IPI; group 2 patients who were also LCT negative but IPI positive. These two groups showed a significantly different history with respect to the number of irreversible immunological transplant rejections. In group 1, 25.3% of the transplanted kidneys had been rejected whereas in group 2, 56.0% of the kidneys had been rejected (p = 5 x 10(-5)). The high incidence of rejections in the group showing only IPI reactions was comparable with that of group 4 comprising patients with concordant IPI and LCT reactions (59.4%). It is inferred from this retrospective study that renal allograft rejection is associated with the development of IPI reactive antibodies which are not detectable by the LCT. The presence of these antibodies prior to transplantation could be detrimental to the transplanted organ. This being the case, the incidence of transplant failures could be reduced by pretransplant screening using the IPI and by avoiding crossmatch positive donors identified by IPI, especially in patients waiting for a retransplantation.

Antibody Specificity↗
PubMed1997

Elevated serum HLA class I levels coincide with acute and chronic graft-versus-host disease.

The ability to predict the likely occurrence of graft-versus-host-disease (GVHD) after BMT would be extremely valuable. We performed a retrospective study on the correlation between soluble HLA class I (sHLA-I) levels and GVHD in the sera of 34 patients receiving an allogeneic BMT and in the sera of 12 patients receiving an autologous BMT. sHLA-I levels measured pre- and at different times post-BMT were correlated with the occurrence of post-BMT complications, ie acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), infections and relapse. No changes in sHLA-I levels (delta sHLA-I) occurred in autologous and allogeneic BMT patients without GVHD. In contrast, sHLA-I reached high levels in patients suffering from GVHD. Increased sHLA-I levels correlated strongly with episodes of both acute and chronic GVHD (P = 0.004 and P = 0.005, respectively). Also during relapse increased sHLA-I levels were found (P = 0.032). During infections sHLA-I levels increased, although not significantly. Kinetic studies gave no evidence that the increase in sHLA-I levels preceded the clinical occurrence of aGVHD or of cGVHD. A slight, but significant correlation was found between total blood bilirubin levels and sHLA-I levels in patients suffering from GVHD (P = 0.037), indicating the contribution of the liver as a source of sHLA-I. We conclude that measurements of sHLA-I levels do not function as a predictive parameter for GVHD, but can be valuable for the monitoring of GVHD after BMT.

Acute Disease↗
PubMed1997

The avidity of allospecific cytotoxic T lymphocytes (CTL) determines their cytokine production profile.

Donor-specific CTL present within the cardiac allograft during a rejection episode are distinct from those that populate the cardiac allograft in the absence of rejection. Whereas the former generally have a high avidity for donor cells, the latter mainly have a low avidity for donor cells. This observation made us reason that high-avidity CTL are implicated in transplant rejection, whereas low-avidity CTL are not. In the present study, we analyse whether both CTL subsets were distinct with respect to their IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) secretion pattern. CTL clones with either a high or a low avidity for donor antigens were stimulated with donor cells, third party cells, or immobilized anti-CD3 MoAb and the amount of cytokine released was measured. High- and low-avidity CTL clones were found to differ with respect to their IFN-gamma production profile. Stimulation with donor cells resulted in IFN-gamma secretion by high-avidity CTL clones, but not by low-avidity CTL clones. CD3 stimulation, in contrast, led to secretion of equivalent amounts of IFN-gamma by both CTL subsets. These observations indicate that low-avidity CTL are fully capable of producing IFN-gamma, but, in contrast to high avidity CTL, fail to do so when they encounter donor cells. As IFN-gamma favours the occurrence of transplant rejection, this observation emphasizes the relevance of high-avidity CTL in the rejection process. Additionally, the data show that the cytokine production profile of CTL depends on the nature of the stimulus.

Antibodies, Monoclonal↗
PubMed1997

Lack of effect of different cytokines on expression of membrane-bound regulators of complement activity on human uveal melanoma cells.

Tumor cells are protected from antibody-dependent complement-mediated lysis by membrane-bound regulators of complement activation (m-RCA). m-RCA are expressed on uveal melanoma cells. We determined whether cytokine treatment affects expression of m-RCA on these cells in vitro. m-RCA expression on uveal melanoma cell lines was studied by flow cytometry, using monoclonal antibodies directed against CD46, CD55, and CD59. Cytokines studied were interferon-alpha (IFN-alpha), IFN-gamma, interleukin-1B (IL-1B), IL-12, and tumor necrosis factor-alpha (TNF-alpha). All three m-RCA were expressed on the uveal melanoma cell lines (CD59>>CD46>CD55), although in variable amounts. With a few exceptions, the cytokines had no effect on m-RCA expression. CD55 expression was not influenced by any of the cytokines. IFN-gamma downregulated expression of CD46 on one cell line (p < 0.01). TNF-alpha upregulated CD59 expression on two of the five cell lines (p < 0.012 and p < 0.001, respectively), which effect was dose dependent. IFN-alpha, IFN-gamma, IL1-beta, IL12, and TNF-alpha had limited effects on m-RCA expression on uveal melanoma cells in vitro.

Antineoplastic Agents↗
PubMed1997

Relation between HLA antigens and skin cancer in renal transplant recipients in Queensland, Australia.

On the basis of previous studies that showed a negative association between HLA-A11 and skin cancer in renal transplant recipients and a positive association with HLA-B27 and HLA-DR7, we performed a study in Queensland with 1098 recipients to address the question of whether the same associations could be found. The influence of HLA mismatching and HLA homozygosity on the risk of skin cancer was also studied. In contrast to earlier studies, HLA-A11 was associated with an increased risk of skin cancer. On the other hand, we confirmed that the HLA-B27 antigen was associated with the development of skin cancer, but only when the development of basal cell carcinomas alone was considered, and we confirmed that there is a weak but not statistically significant association with HLA-DR7. No association between HLA mismatching or HLA homozygosity and the development of skin cancer was observed. Environmental factors such as different levels of exposure to sunlight and infection with human papillomaviruses are factors that are most likely to be involved. We hypothesize that human papillomavirus-induced antigens prevail in the skin cancers in the recipients living in the Netherlands, whereas antigens induced by solar radiation, the so-called "photo-antigens," may be more common in the skin cancers of the recipients living in Queensland. Exposure to sunlight can also induce immunologic unresponsiveness, and excessive exposure to sunlight in Australia may, therefore, simply override the risk factors that are important in countries with a more temperate climate.

Basal Cell Carcinoma↗
PubMed1997

Differential effects of sunscreens on UVB-induced immunomodulation in humans.

Ultraviolet radiation has been shown to suppress the (skin) immune system both in animal species and in humans. Whether sunscreens can prevent immunosuppression is a matter of debate. This study investigated the protective capacity of a commercial sunscreen lotion in humans. Part of the right arm of healthy volunteers was exposed to erythemagenic ultraviolet B doses of 160 mJ per cm2 for four consecutive days. Before irradiation, sunscreen was applied either directly onto the skin or onto a piece of quartz fixed to the skin (to avoid penetration of the sunscreen in the epidermis where it cannot block the photoisomerization of trans-urocanic acid in cis-urocanic acid in the stratum corneum). The control group was irradiated without prior application of sunscreen. Four h after the last irradiation, epidermal sheets were obtained by the suction-blister method from both arms and epidermal cells were used as stimulator cells in the mixed epidermal cell lymphocyte reaction. Responses directed to epidermal cells derived from irradiated skin were expressed as percentages of responses directed to epidermal cells derived from the nonirradiated left arm. The mixed epidermal cell lymphocyte reaction responses in the control group were found to be significantly increased (205%). This enhancement of the mixed epidermal cell lymphocyte reaction responses was associated with an influx of CD36+DR+ macrophages in the irradiated skin. Application of the sunscreen, either onto a piece of quartz or directly onto the skin, prevented the increase of the mixed epidermal cell lymphocyte reaction responses and the influx of CD36+DR+ cells. In an earlier study, volunteers were exposed three times weekly to suberythemagenic doses of ultraviolet B over 4 wk, resulting in mixed epidermal cell lymphocyte reaction responses that were decreased to 20%. The same sunscreen was not able to prevent this suppression. These contradicting results indicate that the protective effect of sunscreens with respect to ultraviolet-induced immunomodulation is critically dependent on the choice of ultraviolet treatment.

Humans↗
PubMed1997

A future for HLA matching in clinical transplantation.

The arguments for and against minimizing HLA antigen mismatching in clinical transplantation have been debated for the past 30 years (Terasaki & Cecka, 1994), but at least two major kidney exchange programmes (EURO- and UK-Transplant), with waiting lists totalling 17 thousand patients, prioritize the least HLA mismatched recipients. In the USA, in the United Network for Organ Sharing (UNOS) zero HLA-A,-B, DR mismatch for exchange of kidneys is mandatory. There is now a clear understanding of the in vivo function of HLA molecules, which have a central role in antigen presentation to T cells and thus initiate the immune response both in the normal individual and in transplant recipients. In the latter case, direct recognition of foreign HLA molecules by recipient T cells is also possible (Shoskes & Wood, 1994). With such a clear understanding of the central functional role for HLA in the immune response, it is not surprising that reports of increased kidney transplant survival correlate with reduced HLA mismatching, and it is of concern that some centres choose to allocate kidneys for transplant ignoring HLA. Reports of benefits of minimizing HLA mismatching in heart (Smith et al., 1995) and lung (Iwaki et al., 1993) transplantation are limited to retrospective studies, and no centre has claimed to allocate these organs taking HLA mismatch into account. Consequently, HLA mismatched thoracic organ transplants predominate, but nevertheless recipients of completely mismatched organs have decreased survivals (Opelz & Wujciak, 1994) and more rejection (Baan et al., 1991; Jarcho et al., 1994). Since transplantation of hearts and lungs is essentially only effective on one occasion, all effort should be made to maximize survival and incorporation of HLA mismatches in allocation criteria for these organs is now overdue (Disesa et al., 1990; Morris, 1994). In this brief review we choose not to cover the extensive literature on the role of HLA mismatching in organ transplantation, but consider the field at the present time with particular emphasis on realistic, practical application of HLA typing to the clinical situation and, in particular, the development of allocation procedures that will best suit the needs of individual patients.

HLA Antigens↗
PubMed1997

Differential suppression of the human mixed epidermal cell lymphocyte reaction (MECLR) and mixed lymphocyte reaction (MLR) by cis-urocanic acid.

Cis-urocanic acid (UCA), formed in the stratum corneum by UV irradiation of trans-UCA has been proposed as a mediator of UV-induced immunosuppression in the skin. In this study, we examined the in vitro effect of cis-UCA (6-100 micrograms/mL) on the human mixed lymphocyte reaction (MLR) and the mixed epidermal cell lymphocyte reaction (MECLR). Addition of cis-UCA (purified or in a mixture with trans-UCA) did not affect the MLR but was able to induce a 20% suppression of the MECLR responses. Because this effect of cis-UCA on the MECLR was not as strong as could be expected from previous in vivo results, we designed a set of experiments in order to enhance the in vitro immunosuppressive capacity of cis-UCA. Firstly, we preincubated epidermal cells with UCA (50 micrograms/mL). for 3 or 6 days before culture in the MECLR because in vivo repeated UV exposure can lead to a photostationary state, where cis-UCA may be present for several weeks. This pretreatment with cis-UCA resulted in a maximal decrease of the MECLR response of 27%, whereas trans-UCA had no effect. Secondly, we investigated whether UVB irradiation of epidermal cells could make cells more sensitive to cis-UCA. However, addition of trans- or cis-UCA did not potentiate the reduced alloactivating capacity of UVB-irradiated cells. Finally, we examined the possibility of a synergistic effect of cis-UCA with histamine. Addition of histamine suppressed the MLR and MECLR responses, but neither cis- nor trans-UCA were able to modulate this decrease. We conclude that cis-UCA can partly downregulate the human MECLR but not the MLR. The mechanism involved in this differential downregulation is not known. In this respect it is striking that cis-UCA dose not potentiate the UVB- or histamine-induced suppression of the MECLR.

Cells, Cultured↗
PubMed1997

In situ action spectra suggest that DNA damage is involved in ultraviolet radiation-induced immunosuppression in humans.

The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to study the immunomodulatory effects of UV radiation. The in vitro action spectrum for the MECLR showed that the UV-induced suppression of the MECLR responses is associated with UV-induced DNA damage. To investigate whether in vivo DNA damage also leads to the abrogation of the MECLR, in situ action spectra were made for the MECLR and the induction of thymine dimers (T < > T). Human skin, obtained from plastic surgery, was exposed to monochromatic light of 254, 297, 302 and 312 nm. After irradiation, epidermal cells were isolated and used as stimulator cells in the MECLR or processed for flow cytometric detection of T < > T. On the basis of dose-response curves for each wavelength, the action spectra for suppression of the MECLR and the induction of T < > T were calculated. These spectra showed close similarities, suggesting that, also in situ, UV-induced DNA damage is involved in the UV-induced suppression of the MECLR. Both action spectra showed a small decline from 254 nm to 302 nm, followed by a steep decline to 312 nm. These data show that, in situ, UVC can efficiently induce DNA damage and modulate cutaneous immune responses.

Cells, Cultured↗
PubMed1997

Cytotoxicity of graft-derived lymphocytes: specific for donor heart endothelial cells?

BACKGROUND: Previously, we showed that lymphocytes cultured from cardiac allografts can lyse lymphoid cell lines from donor origin. Because endothelial cell form the first allogeneic barrier to be encountered in vivo, the reactivity of graft-infiltrating cells against donor heart-derived endothelial cells (DoHEC) may be more relevant for understanding the clinical course after heart transplantation. METHODS: Endomyocardial biopsies (EMB) were taken at different times after transplantation, both during acute rejection and during quiescence. Lymphocytes cultured from these EMB were assayed for cell-mediated cytotoxicity in a 4-hour chromium 51 release test by use of target panels of different cell types derived from donor or third party. Cell specificity was investigated by addition of a tenfold excess of unlabelled target cells to 51Cr-labeled DoHEC. RESULTS: These experiments show that DoHEC can be lysed by lymphocytes derived from EMB. Antigens that were recognized on DoHEC were often donor human leukocyte antigen class I antigens. Some cultures in addition recognized alloantigens present only on DoHEC and not on donor-derived B cells as suggested by lack of or partial inhibition of DoHEC lysis by addition of excess competitor B cells. Endothelial cell-specific reactivity was unequivocally identified after limiting dilution of EMB-derived cultures. CONCLUSION: We conclude that not only DoHEC-reactive but also DoHEC-specific cells are present among the cardiac graft infiltrating cells.

CD8-Positive T-Lymphocytes↗