ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Cellular cytotoxicity toward kidney cell targets has been studied in a model using in vitro cultured canine kidney cells obtained after perfusion trypsinization of kidneys from one-haplotype-mismatched beagles.To study whether cytotoxic effector cells recognize identical antigens on kidney cells as on phytohemagglu-tinin (PHA)-stimulated lymphoblasts, adsorption studies with different monolayers have been performed. Both leukocyte and kidney cell monolayers reduced cytotoxicity against51Cr-labeled PHA-stimulated lymphoblasts very effectively. The average reduction of cytotoxicity was 86% in six consecutive experiments after one adsorption on either one of these two types of target-specific monolayers. Nonspecific monolayers reduced cytotoxicity only for 13%. Specific kidney cell monolayers reduced cytotoxicity against kidney cells almost completely, however leukocyte monolayers reduced cytotoxicity toward kidney cells for only 40%. These results and cold target inhibition data strongly suggest that kidney cells present antigens to which a selective population of cytotoxic T lymphocytes (CTLs) is directed. These CTLs are not cytotoxic for PHA-stimulated lymphoblasts. It is discussed whether the relevant antigens on the kidney cells are organ-specific antigens comparable to the en-dothelial monocyte antigen system as described by Mo-reas and Stastny or that class II antigens are involved in cytotoxicity toward kidney cells.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The immunological responsiveness of a panel of 26 consecutive cadaver kidney allograft patients with good graft tolerance was studied against cells from the specific donor. Among these 26 patients, 11 underwent acute cellular rejection and were studied during the rejection episode. An additional eight transplant patients, who lost their graft as a result of cellular rejection, were nephrectomized and studied 6 months after their return to hemodialysis as the control group of patients “at equivalent risk.” A low responsiveness against the specific donor was observed in cases of good graft tolerance, but was absent during rejection and in the control group. By using mixing experiments, cells from tolerant patients were able to actively and selectively suppress the response of their autologous pretransplant cells stimulated by the specific donor cells. These suppressor cells were effective only when added during the first 48 hr of the culture and could respond at a suppressor to responder cell ratio from 1:1 to 1:4.Finally, our observations indicate that allogeneic un-responsiveness between donor-recipient pairs may be associated with the presence of suppressor cells affecting the generation of helper T cells only in a specific situation, i.e., donor-recipient, and only in cases of good graft tolerance.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Antibodies that react with heterophile transplantation antigens (HTA) have been shown previously not to react with HLA-A, B, or C antigens. This paper presents evidence that anti-HTA does react with a subpopulation of human lymphocytes which is comprised primarily of B cells.Anti-HTA reactivity was removed from sera by absorption with each of three different human B lymphocyte cell lines, but it was unaffected by absorption with platelets or thymocytes. Selected high titer anti-HTA sera absorbed with human platelets, human blood group type AB erythrocytes, and sheep erythrocytes caused lysis of a lymphocyte subpopulation principally composed of B lymphocytes. Absorption of these sera with rat erythrocytes removed both lympholytic activity and anti-HTA activity. Antibody recovered by affinity purification with rat erythrocyte membrane preparations contained both lympholytic and anti-HTA reactivity.These data, considered with previous studies, seem to establish that B cell sensitization may be acquired by a substantial segment of the population by natural immunization from enteric flora and/or by infections with enteric bacteria.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Irradiation of skin with ultraviolet light (UVL) is capable of causing many biological and biochemical changes in this complex organ. One early consequence is the oxidation of epidermal plasma membrane cholesterol, causing the induction of a wide variety of photo-products. It is well recognized that some oxygenated sterols possess potent biological activity on mammalian cells by their ability to inhibit endogeneous mevalonate and cholesterol biosynthesis. In the few immunological systems that have been studied, there is general agreement that lymphocyte function is altered in the presence of certain oxygenated sterols. Insight into the biochemical basis for altered lymphocyte function is lacking, as both afferent and efferent blockades have been suggested.These studies were undertaken to determine the effect of various oxygenated sterols (representing a number of known cholesterol-derived photoproducts) on the generation (afferent) and function (efferent) of cytotoxic T lymphocytes (CTLs). Cell-mediated immune responses which result in the generation of both alloantigen-specific and syngeneic tumor-specific CTLs were evaluated.The results of our studies established the following points: (1) the afferent phase of an immune respone is particularly sensitive to the effects of some cholesterol photoproducts while other oxidized sterol derivatives, known to exist in skin following UVL exposure, have minimal influence on the generation of CTL responses; (2) the only known carcinogenic photoproduct of cholesterol (cholesterol α-oxide) is a very weak inhibitor of lymphocyte function; (3) presentation of oxygenated sterols via liposome membranes is 10-fold more effective than their administration in soluble form; (4) 25-hydroxycholesterol and 20α-hydroxycholesterol were found to be the most potent inhibitors, causing a parallel depression in lymphocyte proliferation, CTL activity, and endogeneous sterol biosynthesis, and (5) 7β-and 7α-hydroxycholesterol functioned in a unique manner, causing an abrogation of CTL activity without depressing proliferative responses and endogeneous sterol biosynthesis to a significant degree.These studies represent the first time that an attempt has been made to evaluate a possible biochemical basis for immune suppression known to precede experimental UVL carcinogenesis. Our results suggest that some, but not all, of the oxidation products of cholesterol found in skin following UVL irradiation exert an influence on immune responses. Derivatives of cholesterol could be partially responsible for the alterations in immunological potential of the UVL-exposed host. The induced presence of an inhibitor of CTL differentiation or function at a time following UVL tumor emergence may play a role in this process by providing an early tumor escape mechanism.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Two parameters of enhancing major histocompatibility complex (MHC) antibodies, previously separately studied, namely, Ig class and antigen specificity, have been treated simultaneously. In the experimental model used, Sa 1 tumor cells, indigenous of A/J (H-2a) were grafted on CBA (H-2k) or C57BL/Ks (H-2d) mice. Immune sera specific for the H-2 K/D- or H-2 I-coded antigens of the A/J haplotype (anti-Kk, or IAk, IBkIJkIEk, or ICd, Sd, Gd, or Dd) and their immunoglobulin fractions (separated on protein A-Sepharose columns) were injected either i.v. or locally as a mixture with the challenging Sa 1 cells.Within the limits of the studied system, the following results were obtained: (1) Sa 1 cells do possess Iakantigens at their surface detected by C-dependent cytotoxicity; no ICd, Sd, or Gdproducts were detected. (2) The bulk of enhancing activity is concentrated in IgG1 anti-K/D antibodies (anti-Ddwhen Sa 1 was grafted on CBA mice and anti-Kk, on C57BL/Ks). (3) Anti-Iakantibodies have some activity on Sa 1 cells grafted on C57BL/Ks mice. This activity is significant for IgG1 anti-Iakand suggestive for IgG2 of the same specificity. (4) No enhancing activity was detected in the other antibodies: IgG2 anti-Dd, IgG2 anti-KkIgG1, or IgG2 anti-ICd, Sd, Gdas well as in fractions containing IgM and IgA antibodies directed against any studied portion of the MHC products. These results are discussed in terms of the mechanisms involved in enhancement.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Twenty-seven patients (age range from 1 to 55 years) were included in a cooperative bone marrow transplantation program in Stockholm. Of eight patients with severe aplastic anemia (SAA), two died following graft rejection and six (75%) are alive between 3 months and 4½ years after transplantation. Two patients with end stage leukemia died of septicemia and bleeding shortly after transplantation. Thirteen of 17 patients (76%) with acute leukemia in their first or second remission are alive 1 to 16 months after transplantation. Death was caused by septicemia in two patients, interstitial Candida pneumonitis in one and gastrointestinal bleeding in association with graft-versus-host disease in one. Among the leukemic patients all deaths occurred in subjects over 17 years of age and all 10 children are alive. No relapse has yet been seen. Successful bone marrow transplantations were carried out utilizing ordinary hospital resources only. This justifies the practice of performing transplantations in subjects with SAA and acute leukemia in remission even outside specially equipped and designed bone marrow transplantation units.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The reproducibility of the measurement of concanavalin A (Con A)-inducible suppressor cell activity in human peripheral blood lymphocytes was examined. Suppressor cells were activated for 24, 48, or 72 hr with 3, 6, and 12 μ of Con A (Con A in concentrations greater than 12 μ/ml was toxic to the lymphocytes) per ml and suppression of the proliferative response of autologous lymphocytes to varying concentrations of Con A (3, 6, and 12 μ/ml) was measured. No single set of conditions consistently produced optimal suppression. Assays performed concurrently using lymphocytes from the same subject produced comparable suppressor cell activity; however, considerable variability in suppressor cell activity was observed under all conditions tested when five normal subjects were examined on as many as four separate occasions. The variability was reduced but not eliminated by reporting the data for each assay in terms of a peak suppression value determined from multiple sets of conditions. The results suggest that small differences in suppressor cell activity between patient groups may be masked by the intrinsic variability of the assay system.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Suppressor cells, which in an alloantigen-specific manner inhibit proliferation of donor cells to host antigens in a mixed lymphocyte culture and adoptively transfer the suppression of graft-versus-host disease (GVHD), undergo a gradual clonal reduction in long-term, allogeneic, histoincompatible rat radiation chimeras until they can no longer be measured in an in vitro suppressor cell assay. When lymphohematopoietic cells from these chimeras are transferred into lethally irradiated secondary recipients of original donor strain, the suppressor cells, now in a target antigen-free environment, undergo a further clonal reduction. After “parking” for 120 days, the chimeric cells are specifically tolerant to original host antigens, but cannot adoptively transfer suppression of GVHD. When chimeric cells, parked for 120 days in secondary recipients of original donor strain, are stimulated with original host-type antigen repeatedly during or once at the end of the parking period, the suppressor cell clone is expanded, suppressor cells can be identified in vitro, and suppression of GVHD can adoptively be transferred to tertiary recipients.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The results of 370 transplants done at 11 transplant centers in Los Angeles over the past 4 years is summarized for DR matching and transfusions. Among 28 patients with two HLA-DR antigens matched, the 1-year transplant survival rate was 75% as compared with 47% for those patients with no matched HLA-DR antigens (P< 0.0025). Therefore, in this multicenter single-typing laboratory trial, HLA-DR typing had a significant effect on transplant outcome. The effect of pretransplant transfusions was additive. Patients with fewer than five transfusions had a 1-year survival rate of 45% compared with 69% for those with five or more transfusions (P< 0.0005). In patients with two DR antigens matched and five or more transfusions, the survival rate was 86%. Similarly, patients with zero or one DR antigen match had a higher graft survival rate if they had previously been transfused with more than four units of blood. We conclude that two-DR antigen-matched transplants have a higher chance of success than those with a zero or one antigen match and that this effect is additive with transfusions.

ISSN:0041-1337    

出版商:OVID    

年代:1982

数据来源: OVID