CD+4 CD+25调节T细胞的生物学功能及其在移植物抗宿主病中作用的研究进展

 CCD+4 CD+25 调节T（Treg）细胞具有免疫无能性和免疫抑制性两大功能特征,是抑制性T细胞的一种亚群。能抑制效应细胞CD+4 T细胞和CD+8 T细胞的活化与增殖,从而有效抑制免疫系统对外来器官产生的排异反应,减轻了造血干细胞移植（HSCT）术后移植物抗宿主病（GVHD）,而且不影响移植物抗白血病（GVL）效应,从而在移植免疫耐受中发挥重要的作用。     

异基因造血干细胞移植治疗多发性骨髓瘤研究进展

异基因造血干细胞移植（allo-HSCT）是唯一可能治愈多发性骨髓瘤（MM）的方法,但较高的移植相关死亡（TRM）率限制了其应用。尽管减低强度预处理（RIC）的allo-HSCT降低了TRM率,但其疗效仍不优于自体造血干细胞移植（auto—HSCT）。因此需要进一步研究降低移植毒性和促进移植物抗骨髓瘤（GVM）效应的新策略,以便使RIC allo-HSCT更加安全有效。文章对目前allo—HSCT在MM中的研究进展进行了综述。     

DC细胞刺激γδT细胞扩增诱导干细胞移植时GVL研究

目的：研究γδT细胞的体外生存期,抗白血病活性及可能引起的GVHD,为将来自体及异体移植后输注γδT细胞诱导GVL作前期基础研究。方法：对移植患者采集物用GM－CSF＋IL－4进行培养,使其分化和扩增为DC;然后用DC和细胞因子IL－2刺激其CD4^ T细胞扩增后,协同DC共同刺激γδT细胞扩增,进而用MTT比色法和CFU－GM集落培养研究其功能。结果：γδT细胞能在体外长期大量扩增。扩增的γδT细胞对多咱白血病细胞株具有杀伤作用,而对自体及异体CFU－GM集落形成能力无显著影响。结论：γδT细胞可望用于造血干细胞移植后的过继免疫治疗,值得进一步做有关临床研究。     

CD34+造血干细胞阳性提取进行异基因造血干细胞移植

CD34抗原在造血干细胞中有表达,因而将提取的CD34+造血细胞进行造血干细胞移植是可能的,是合理的,CD34阳性细胞的提取及移植是有其特点的,这样的异基因造血干细胞移植已有不少成功的报告,现将其主要方法介绍如下.     

减轻异基因造血干细胞移植GVHD增强GVT的研究

异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)是一种有效治疗恶性肿瘤及非恶性疾病的方法,近年来成为治愈某些恶性血液性肿瘤疾病的主要手段之一,明显提高了患者的长期生存率[1];但移植物抗宿主病(graft-versus-host disease,GVHD)仍然是allo-HSCT的主要并发症,是移植相关死亡及影响患者生存质量的重要原因。GVHD是由移植物中所含供者T细胞识别宿主抗原而攻击宿主组织器官所产生的病理损伤,并导致宿主多脏器损伤的一个疾病过程。以T细胞为靶点的免疫抑制剂及T细胞去除术的应用是目前GVHD…     

HLA-CW基因分型在造血干细胞移植中的意义探讨

目的探讨HLA-CW位点基因分型在造血干细胞移植(hematopoicetic stem cell transplantation-HSCT)中的作用,对HLA-CW基因位点相合与不相合造血干细胞移植的效果进行分析.方法采用聚合酶链反应-序列特异性引物扩增(polymerase chain reaction-sequence specific primers,PCR-SSP)方法对HSCT供、受体共42个样本进行HLA-CW位点等位基因分析.结果HLA-CW基因全相合者9例造血重建,存活200 d以上7例,1例存活303d复发,2例存活44 d(死于感染),无病生存率(66.7±3.4)%.1例(11.1%)发生急性移植物抗宿主病(aGVHD),3例(33.3%)发生慢性移植物抗宿主病(cGVHD).HLA-CW基因不相合者12例造血重建,存活200 d以上6例,1例存活105 d复发,6例存活75 d死亡,无病生存率(41.7±5.4)%(P＜0.05).6例(50%)发生aGVHD;5例(41.7%)发生cGVHD(P＞0.05).结论HLA-CW基因不相合导致的aGVHD及相关死亡率明显高于CW基因相合者,显示CW基因不相合也是造成aGVHD发生率增高和影响移植效果的重要因素.     

小剂量环孢素预防异基因外周血造血干细胞移植中的移植物抗宿主病

目的 :评价小剂量环孢素预防异基因外周血造血干细胞移植中移植物抗宿主病 (GVHD)的有效性、安全性。方法 :观察 30例采用小剂量环孢素预防GVHD的异基因外周血造血干细胞移植患者。小剂量环孢素的用法 :2～ 3mg/ (kg·d) ,静脉注射 ,移植前 1天～移植后 10天 ,此时患者能口服时改为 6mg/ (kg·d)口服 ,10周后按每周 5 %量递减 ,直至移植后 183天。结果 :所有患者均获造血重建 ,仅有 1例发生Ⅰ度急性GVHD ,3例出现慢性GVHD ,经治疗后均缓解。小剂量环孢素的副作用少而轻。结论 :小剂量环孢素在预防异基因外周血造血干细胞移植的GVHD疗效可靠 ,用药安全     

移植物NK和T细胞上抑制型受体表达对异基因造血干细胞移植后影响的观察

目的:探讨异基因造血干细胞移植(allo-HSCT)中移植物和移植后1个月患者外周血NK细胞和T细胞上4种抑制型受体(CD158a、CD158b、NKB1及CD94/NKG2A)的表达对造血重建及急性移植物抗宿主病(aGVHD)的影响.方法:对29例接受异基因造血干细胞移植的患者进行研究,采用流式细胞术检测移植物和移植后1个月患者外周血中NK细胞及T细胞上4种抑制型受体的表达,分析其对造血重建及aGVHD的影响.结果:移植物中NK细胞上CD158a、NKB1、CD94/NKG2A的表达在Ⅱ～Ⅳ度aGVHD组分别为(4.36±4.54)％、(1.37土3.24)％和(9.56±8.98)％,明显高于0～Ⅰ度aGVHD组的(0.52±0.51)％、(0.56±0.97)％和(1.85±1.71)％,P值均＜0.05;而CD8+T细胞上CD94/NKG2A的表达在0～Ⅰ度aGVHD组明显高于Ⅱ～Ⅳ度aGVHD组,分别为(25.67±14.66)％和(11.80±8.09)％,P＜0.05.结论:Allo-HSCT移植物中NK细胞高表达CD158a、NKB1和CD94/NKG2A时可能增加Ⅱ～Ⅳ度aGVHD的发生率,而CD8+T细胞上高表达CD94/NKG2A可能降低Ⅱ～Ⅳ度aGVHD的发生率.     

异基因造血干细胞移植相关研究进展

近年来,单倍体相合造血干细胞移植的发展使“人人都有移植供者”成为现实.因此,选择合适的供者以及解决移植相关并发症,如促进植入、降低移植后移植物抗宿主病的发生率和复发率成为改善移植预后的关键问题.文章介绍了异基因造血干细胞移植的相关研究进展.     

自体外周血干细胞加激活骨髓联合移植治疗T细胞淋巴瘤的诱导移植物抗宿主病

 目的　研究自体造血干细胞（APBSC）加激活骨髓（ABM）联合移植治疗淋巴瘤过程中ABM诱导移植物抗宿主病（GVHD）的作用。方法　一例T免疫母细胞非霍奇金淋巴瘤（NHL）患者行APBSC+ABM联合移植治疗,观察皮疹、腹泻及黄疸的发生。结果　皮肤出现Ⅰ～Ⅱ度GVHD改变,无腹泻及黄疸,已无瘤生存13年。结论　APBSC加ABM联合移植能诱导GVHD,并获得长期无病生存的疗效。     

Helper function of memory CD8+ T cells: heterologous CD8+ T cells support the induction of therapeutic cancer immunity

In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNgamma-producing memory CD8+ T cells act as "helper" cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type "heterologous" (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and helper functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of helper functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections.     

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

Background  

Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro -generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear.     

CD+4CD+25调节性T细胞与肿瘤免疫

 近期研究发现一个有独特免疫调节功能的T细胞亚群：CD+4 CD+25调节性T细胞,不仅能抑制自身免疫性疾病发生,还参与肿瘤免疫的调节。这群细胞具有免疫无能和免疫抑制特性,与肿瘤免疫逃逸有密切的关系。肿瘤环境中CD+4 CD+25调节性T细胞增加,导致肿瘤免疫失调,去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供了一种新的思路。     

Health psychology and distress after haematopoietic stem cell transplantation

The purpose of this study of 23 adult haematopoietic stem cell transplantation (HSCT) recipients is to compare the presence of post-transplantation depression disorders by gender and to compare the outcomes among those with and without depressive disorders using a health psychology focus. This cross-sectional pilot study of mid-term survivors took place in hospital outpatient clinic. Main outcome measures are depression disorders, health status (Short Form-12) and health anxiety. Female survivors had a higher rate of depression disorders, but those with treated depressive disorders were similar to those without depression on health-related quality of life and health anxiety. Neither patient age nor time since HSCT was associated with depressive disorders. A health psychology approach may enhance management of HSCT survivorship.     

CD4+CD25+ regulatory T cells in human hematopoietic cell transplantation

Naturally occurring CD4+CD25+ regulatory T cells (T(reg)) are differentiated T lymphocytes actively involved in the control of peripheral immunity. Over the past few years, a number of animal studies have demonstrated the critical role of these cells in the outcome of allogeneic hematopoietic stem cell transplantation (HCT). In these models, T(reg) can exert a potent suppressive effect on immune effector cells reactive to host antigens and prevent graft versus host disease (GVHD) while preserving the graft-versus-leukemia effect (GVL). The present review summarizes current knowledge on the role of T(reg) populations in humans following allogeneic HCT. Recent investigations focusing on T(reg) in transplant patients have generated conflicting results mostly due to the use of different parameters to assess T(reg). Nonetheless, these studies suggested that an imbalance between T(reg) and effector cells during immune reconstitution can substantially impair regulatory mechanisms and contributes to the development of GVHD. Building on these studies, a number of therapeutic strategies are being developed to positively modulate T(reg) pools in vivo and prevent or even correct GVHD. Conversely, clinical interventions can also be envisaged to decrease T(reg) activity in vivo and enhance the GVL effect. These potential strategies are discussed herein. Coming years will undoubtedly yield additional knowledge on how to use T(reg) subsets in vivo and successfully control and modulate immune responses in patients post-HCT.     

Antigen-specific CD4+ T-cell help is required to activate a memory CD8+ T cell to a fully functional tumor killer cell

Although the importance of CD4+ T-cell help for generation of an effective CD8+ effector cytotoxic T cell (CTL) response is well established, the role of T-cell help in the activation of memory T cells to become fully functional tumor killer cells is undefined. Using synthetic peptide immunizations corresponding to the major CTLs and T-helper epitopes of ovalbumin, adoptive transfers of ovalbumin-specific memory CTLs (mCTLs), and ovalbumin as the tumor-specific antigen in a mouse tumor model, we have determined that T help is essential for the activation of mCTLs to kill tumors. Our data show that T-helper cells specific for the tumor-associated antigen are required for the reactivation of mCTLs by antigen presented indirectly from tumor. In contrast, effector CTLs do not need T help to kill tumors. These results have implications for induction of tumor immunotherapy by immunization.     

Co-immunization with L-Myc enhances CD8+ or CD103+ DCs mediated tumor-specific multi-functional CD8+ T cell responses

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c⁺ DCs, CD8⁺CD11c⁺ DCs and CD103⁺CD11c⁺ DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8⁺ T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8⁺ T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8⁺ T cells or CD8⁺CD11c⁺ DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8⁺ DCs and CD103⁺ DCs mediated CD8⁺ T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8⁺ T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8⁺ DCs and CD103⁺ DCs mediated tumor-specific multi-functional CD8⁺ T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.