Autologous Mixed Lymphocyte Reaction in Man

The proliferative response of T lymphocyte cultured with autologous non-T lymphocyte is known as the autologous mixed lymphocyte reaction (AMLR). In AMLR, both helper and suppressor functions are generated. In this investigation we have examined T cell proliferative responses in AMLR in 12 patients with bronchial asthma, 10 patients with allergic rhinitis, and 10 patients with atopic dermatitis and compared that with simultaneously studied healthy controls. Our data show that the T cell proliferation in AMLR in patients with bronchial asthma is significantly higher than that of healthy normals. However, AMLR response in patients with allergic rhinitis or atopic dermatitis is comparable to controls. Mechanisms for increased AMLR in patients with bronchial asthma are discussed.     

Effect of Neuraminidase on the Rat One-Way Mixed Lymphocyte Interaction

The effect of Vibrio cholerae neuraminidase (VCN) on the rat one-way mixed leukocyte interaction (MLI) was investigated. VCN was iodinated without apparent loss of biological activity. Treatment of stimulatory cells with either cold or ¹²⁵I-labeled VCN significantly enhanced their subsequent reactivity in the MLI. In contrast, treatment of the responding cells alone did not increase the response. Our studies rule out the possibility that VCN increases cellular immunogenicity by binding to the lymphocyte surface. The mechanism of VCN action appears to involve a direct surface modification of lymphoid cells; this modification leads to their increased reactivity.     

Effect of Neuraminidase on the Rat One-Way Mixed Lymphocyte Interaction

The effect of Vibrio cholerae neuraminidase (VCN) on the rat one-way mixed leukocyte interaction (MLI) was investigated. VCN was iodinated without apparent loss of biological activity. Treatment of stimulatory cells with either cold or ¹²⁵I-labeled VCN significantly enhanced their subsequent reactivity in the MLI. In contrast, treatment of the responding cells alone did not increase the response. Our studies rule out the possibility that VCN increases cellular immunogenicity by binding to the lymphocyte surface. The mechanism of VCN action appears to involve a direct surface modification of lymphoid cells; this modification leads to their increased reactivity.     

Autologous Mixed Lymphocyte Reactions in Patients with Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis: Both Non-T Cells and in-Vivo-Activated T Cells Can Act as Stimulator Cells

The lymphocyte responses in autologous mixed lymphocyte reactions (AMLR) between irradiated non-T and T lymphocytes from the peripheral blood (PB) of rheumatoid arthritis (RA) and juvenile RA (JRA) patients were decreased compared with the AMLR responses of normal PB lymphocytes. Normal AMLR responses were seen in the synovial tissue and the synovial fluid lymphocytes from RA and JRA patients. The lymphocyte responses were also decreased in AMLR between irradiated non-T cells from peripheral blood and T cells from synovial tissue (ST) in RA patients and between irradiated non-T from PB and synovial fluid (SF) T cells in JRA patients. However, when irradiated non-T cells from ST of RA patients or from SF of JRA patients were mixed with autologous PB T lymphocytes, increased lymphocyte responses were observed. SF T lymphocyters and ST T cells were also shown to stimulate autologous PB T lymphocytes.     

Catalase and Lipopolysaccharide Enhance Proliferation in the Rat Mixed Lymphocyte Reaction

Proliferation of rat spleen cells in a mixed lymphocyte culture was amplified fivefold or more in the presence of 2000 units of catalase/ml, as measured by [3H]thymidine incorporation. A similar effect was observed with 1 microgram of lipopolysaccharide (LPS)/ml. Addition of polymyxin B abrogated the promotional effect of LPS, but not that of catalase. These results indicate that the hydrogen peroxide generated by some cells in the rat spleen cell mixed lymphocyte culture suppresses the proliferative response. The demonstration that removal of plastic adherent cells (reducing the percentage of monocytes/macrophages by 75-80%) also results in a 5- to 10-fold increase in a subsequent MLR, indicates that some of the adherent cells may be the producers of hydrogen peroxide, which at higher concentrations suppresses the T-cell proliferation. The enhanced proliferation was not mainly due to increased interleukin 2 (IL-2) production, since the IL-2 concentrations of catalase and LPS-containing cultures were lower than those of control cultures.     

乙型慢性活动性肝炎患者自身TA-T混合反应及其对自身B细胞功能调理的研究

对10例乙型慢性活动型肝炎患者(CAH)进行自身TA-T淋巴细胞混合反应（TA-TAMLR)及其对自身B细胞功能调理的空斑形成细胞(PFC)的研究结果表明，CAH的PFC抑制率明显低下，此现象与TA-TAMLR低下密切相关，加入外源性白细胞介素-2（IL-2)后，两者反应均有所增强，但仍明显低于10例正常对照组。     

Defects of Autologous Mixed Lymphocyte Reaction-Activated Immunoregulatory T Cells in Patients with Systemic Lupus Erythematosus

The present study was undertaken to determine the nature of the immunoregulatory T-cell defect after autologous mixed lymphocyte reaction (AMLR) activation in patients with systemic lupus erythematosus (SLE). Although AMLR was decreased in patients with SLE compared with normals, there was no difference in major proliferative cells (T4 cells and T4+JRA+ subset) in response to AMLR. Functional activity of AMLR-stimulated T4 subsets in patients with SLE and normals was examined in helper and suppressor/inducer assay, using pokeweed mitogen (PWM)-driven IgG synthesis. The T4+JRA- (helper) subset from SLE patients showed no greater activity than normals. However the T4+JRA+ (suppressor/inducer) subset from SLE patients showed decreased suppression induction compared with normals. This defect in the suppressor/inducer function was demonstrated even in patients with inactive SLR or in remission.     

Flow Cytometric Analysis of Lymphocyte Activation in the Mixed Lymphocyte Response

Interleukin 2 receptor (IL2R) expression may be a useful parameter for assessing lymphocyte activation in the mixed lymphocyte response (MLR). However, the contribution of irradiated stimulator (S*) cells to the levels of IL2R⁺ cells recovered must first be defined. We have used a flow cytometric parameter termed the sip count to assess this potential contribution of S* cells. This parameter, which is the number of cells within a defined cell gate, is a reflection of the viable cell number per culture well, since (a) a constant number of cells were plated per well on day 0, (b) cells recovered from a well were resuspended in a constant volume, (c) the flow cytometer aspirated (sipped) a constant volume of cell suspension, and (d) nonviable cells were not included in the gate. Sip count assessment showed that only 5% of S* cells were recoverable by day 4 of culture; in contrast, 70% or more of unstimulated responder cells were recoverable. Sip counts of MLR cultures identified an increase in cell number beginning on day 5, reflecting DNA synthesis and cell division. We then used the sip count to assess changes in the levels of IL2R⁺ cells in MLR cultures. The number of IL2R⁺ cells continued to increase up to day 7, even though maximal DNA synthesis occurred on day 5. Further, dual color analysis revealed that the proportion of CD4 cells expressing IL2R was maximal on day 5, whereas the proportion of CD8 cells expressing IL2R continued to increase until day 9. These findings show that flow cytometry can be used to study lymphocyte activation by alloantigens.     

At Least Two Loci of the Major Histocompatibility Complex Can Determine Mixed Lymphocyte Stimulation in the Rat

Analysis of a recombinant haplotype of the major histocompatibility complex showed that two genetically separable loci (or groups of loci), LD--1 and LD--2, determine mixed lymphocyte stimulation in the rat. LD--1 maps into the H--1B region which contains the Ir genes and is associated with strong, mixed lymphocyte stimulation. LD--2 maps into the H--1A region and determines weak stimulation. LD--1 and LD--2 determinants can be detected by primed lymphocyte typing.     

自体脂肪移植在上睑凹陷填充术中的临床应用

目的：探讨自体脂肪颗粒注射填充矫正上睑凹陷的临床效果。方法首先在患者脂肪丰厚的部位,注射器抽取脂肪颗粒,经清洗液反复冲洗后,将脂肪颗粒注入上睑凹陷区。结果本组共18例,14例一次注射充填后形态满意,4例有部分吸收,行二次注射。结论上睑凹陷畸形采用自体脂肪颗粒填充矫正,方法简单,安全有效。     

Effect of Interferon on Cell Proliferation and Generation of Cytotoxic Potential in Mixed Autologous and Allogeneic Lymphocyte Cultures

Autologous and allogeneic mixed lymphocyte cultures (AMC and MLC) were assayed for blastogenesis, generation of cytotoxic potential, and the effect of interferon (IFN-alpha) on these features. The cells of the mixed cultures lysed K562, Daudi, and autologous and allogeneic phytohaemagglutinin blasts. Stimulator-specific cytotoxicity was observed only in MLC. B blasts induced with Staphylococcus aureus were only affected in a stimulator-specific manner. Short-term IFN treatment of the MLC-derived effectors before the lytic assay enhanced the nonspecific component of cytotoxicity. Cell proliferation was considerably lower in AMC than in MLC. This was decreased when IFN-alpha was added at the initiation of the cultures. The presence of IFN influenced the generation of lytic potential. Comparison of the lysis of the different targets exerted by MLC-activated cells suggested that the specific component was more substantially elevated than the nonspecific one. It is likely that the IFN induced such modifications in the culture conditions that favoured the proliferation of the specific clone. Re-exposure of lymphocytes cultured in the presence of IFN to another dose of IFN before the assay had no influence on their lytic potential.     

The Role of Salvage Second Autologous Hematopoietic Cell Transplantation in Relapsed Multiple Myeloma

Multiple myeloma (MM), a malignant disorder of plasma cells affecting primarily elderly patients, is the second most commonly diagnosed hematologic neoplasm. With the recent influx of effective new agents available, including proteasome inhibitors, immunomodulators, targeted monoclonal antibodies, and now chimeric antigen receptor T cell (CAR-T) therapy, the treatment landscape is evolving rapidly. Although the role of consolidative autologous stem cell transplantation (ASCT) in first remission is well established, in the relapsed setting after upfront ASCT, the role of a second ASCT (SAT) following reinduction is less clear and understudied. Practice patterns vary significantly across institutions, and most of the literature available to guide clinical decisions consists of single-institution experiences, with only 1 randomized study evaluating the role of SAT compared with a nontransplantation approach. SAT is likely underused, because it has not been included in clinical trials examining novel regimens for relapsed disease. Furthermore, outcomes likely can be improved with approaches to intensify the preparative regimen and the use of standard post-transplantation maintenance. In this review, we examine the role of SAT in the current MM treatment landscape in the context of recent data on the efficacy of CAR-T therapy in this disease. We caution the abandonment of SAT, given that CAR-T therapy is in its infancy in MM treatment, and that real-world data in the relapsed setting are consistently inferior to clinical trial outcomes.     

Application of a Novel Diagnostic Rule in the Differential Diagnosis between Acute Gouty Arthritis and Septic Arthritis

Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to < 8) and low probability (≤ 4). In this retrospective study, we applied this diagnostic rule to 136 patients who presented as acute monoarthritis and were subsequently diagnosed as acute gout (n = 82) and septic arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P < 0.001). Patients with acute gout had significantly more ''high'', and less ''low'' probabilities compared to those with septic arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.

Graphical Abstract

相似文献   

The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV

The factors controlling epitope selection in the T cell response to persistent viruses are not fully understood, and we have examined this issue in the context of four HLA-B*35-binding peptides from the pp65 antigen of human cytomegalovirus, two of which are previously undescribed. Striking differences in the hierarchy of immunodominance between these four epitopes were observed in healthy virus carriers expressing HLA-B*3501 versus B*3508, two HLA-B allotypes that differ by a single amino acid at position 156 (HLA-B*3501, (156)Leucine; HLA-B*3508, (156)Arginine) that projects from the alpha2 helix into the centre of the peptide-binding groove. While HLA-B*3501(+) individuals responded most strongly to the (123)IPSINVHHY(131) and (366)HPTFTSQY(373) epitopes, HLA-B*3508(+) individuals responded preferentially to (103)CPSQEPMSIYVY(114) and (188)FPTKDVAL(195). By comparing peptide-MHC association and disassociation rates with peptide immunogenicity, it was clear that dissociation rates correlate more closely with the hierarchy of immunodominance among the four pp65 peptides. These findings demonstrate that MHC micropolymorphism at positions outside the primary anchor residue binding pockets can have a major impact on determinant selection in antiviral T cell responses. Such influences may provide the evolutionary pressure that maintains closely related MHC molecules in diverse human populations.     

Autologous mixed lymphocyte responses in experimentally-induced arthritis of the Lewis rat

Lewis rats develop immune-mediated arthritis following injection with a variety of agents including bovine type II collagen (bCII), mycobacteria, muramyl dipeptide and CP20961. Since susceptibility to experimentally-induced arthritis has been linked to the genes encoding the major histocompatibility complex, it is hypothesized that antigen presentation to autoreactive T-cells is a critical event in the pathogenesis of disease. T-cells, isolated from Lewis rats immunized with bCII or mycobacteria, were co-cultured with splenic or thymic antigen presenting cells (APC) and proliferative responses to antigen were assessed by 3H-thymidine incorporation. T-cell proliferation was observed upon culture with APC without requiring the addition of antigen. T-cells from rats injected with non-immunogenic adjuvants also demonstrated an increased autologous MLR compared to T-cells from non-injected animals. In contrast, T-cells from animals immunized with non-arthritogenic antigens, including ovalbumin or tetanus toxoid, proliferated only when co-cultured with specific antigen-pulsed APC. These results suggest that immunization with arthritogens activates a population of self-reactive T-cells, which respond in an autologous MLR. We propose that these autoreactive T-cells recognize endogenously-derived self peptides rather than peptides derived from a joint autoantigen.     

Outcome of a Salvage Third Autologous Stem Cell Transplantation in Multiple Myeloma

To evaluate the outcomes of salvage third autologous stem cell transplantation (ASCT) in patients with relapsed multiple myeloma. We analyzed 570 patients who had undergone a third ASCT between 1997 and 2010 (European Society for Blood and Marrow Transplantation data), of whom 482 patients underwent tandem ASCT and a third ASCT at first relapse (AARA group) and 88 patients underwent an upfront ASCT with second and third transplantations after subsequent relapses (ARARA group). With a median follow-up after salvage third ASCT of 61 months in the AARA group and 48 months in the ARARA group, the day +100 nonrelapse mortality in the 2 groups was 4% and 7%, the incidence of second primary malignancy was 6% and 7%, the median progression-free survival was 13 and 8 months, and median overall survival (OS) was 33 and 15 months. In the AARA group, according to the relapse-free interval (RFI) from the second ASCT, the median OS after the third ASCT was 17 months if the RFI was <18 months, 37 months if the RFI was between 18 and 36 months, and 64 months if the RFI was ≥36 months (P?<?.001). In the ARARA group, the median OS after the third ASCT was 7 months if the RFI was <6 months, 13 months if the RFI was between 6 and 18 months, and 27 months if the RFI was ≥18 months (P?<?.001). In a multivariate analysis of the AARA group, the favorable prognostic factor was an RFI after second ASCT of ≥18 months. Progressive disease and a Karnofsky Performance Status score of <70 at third ASCT were unfavorable factors. A salvage third ASCT is of value for patients with relapsed myeloma, particularly for those with a long duration of response and chemosensitive disease at the time of transplantation.     

Transitivity of Response in the Mixed Lymphocyte Culture Test

We present a model of mixed lymphocyte culture (MLC) response which assumes one specificity per locus. It also assumes that an animal A will fail to stimulate animal B if, and only if, the set of specificities possessed by A is a subset of the set of specificities in B. The last assumption implies that non-stimulation is transitive; that is, if A does not stimulate B, and B does not stimulate C, then A will not stimulate C. The inclusion of antigenic sets can be used to partially order the animals in a hierarchy. Partial ordering can detect multiple lymphocyte-defined (LD) loci with relative ease; it indicates the number of antigens present in particular individuals; and it detects exceptions to the rule of transitivity which may expose immune response genes, minor loci, or other mechanisms that affect MLC response. This analytical procedure is most useful when testing half-sib families or hybrids sharing a common parental strain. We have applied this procedure to the MLC in cattle half-sib families and found that the data strongly support the existence of at least four LD loci.     

Searching for the Cartilage-associated Mimicry Epitope in Adjuvant Arthritis

Adjuvant arthritis (AA) is a T cell mediated disease which can be induced in genetically susceptible rats by immunization with heat-killed Mycobacterium tuberculosis ( Mt ) suspended in incomplete Freund's adjuvant. The critical mycobacterial T cell epitope for the induction of AA was previously identified as residues 178-186 of the mycobacterial 65 kDa heat shock protein ( Mt. hsp65 178-186 ). It was suggested that the development of AA was due to molecular mimicry between a mycobacterial epitope and a cartilage-associated self-antigen. However, until now such cartilage-associated mimicry epitope has not been identified. In this study we designed a computer search profile to predict mimicry self-epitopes, and investigated whether one or more of these self-epitopes could serve as mimicry epitopes in AA. Although several of these self-epitopes were recognized by arthritogenic T cells, no cross-reactivity was found between T cells specific for these self-epitopes and Mt. hsp65 178-186 specific T cells.     

Arthritis patient education: A review of the literature

Arthritis in one of the most prevalent chronic diseases and the number one disabler of the elderly. Even though arthritis is a major cause of morbidity and a contributor to early mortality, relatively few studies have been undertaken to examine effects of arthritis patient education. This review was undertaken to (1) provide a summary of arthritis patient education studies, (2) summarize the effectiveness of arthritis patient education in changing knowledge, behavior, psychological status, and health status, (3) address critical issues/problems in arthritis patient education study methodology, and (4) suggest guidelines for future design, implementation, and evaluation of arthritis patient education programs. In addition, we discuss implications of past studies for future practice.