不同原位肝移植模型大鼠的CD4~+CD25~+调节性T细胞数量变化的研究

目的建立稳定的大鼠原位肝移植模型,并检测大鼠外周血中CD4+CD25+调节性T细胞(regulatory T cells,Treg)比例的变化。方法采用近交系成年雄性BN、LEW大鼠,改良"二袖套"法建立肝移植模型31例。术前随机分为3组:排斥组(LEW→BN,n=9),耐受组(BN→LEW,n=11),同基因组(BN→BN,n=11)。存活的受体分别于术后5 d、10 d、30 d取外周血,分离外周血中的单个核细胞,由流式细胞仪检测CD4+CD25+Treg比例。并于相应时间点每组随机各处死2只,取肝脏标本观察病理学变化。每组选取5例来观察生存期,存活>100 d时各处死2只,取肝脏标本。结果中位生存期:排斥组14 d,耐受组112 d,同基因组129 d。耐受组与同基因组术后未见明显排斥反应。术后7 d,排斥组肝脏病理Banff评分Ⅲ级。肝移植早期,排斥组和自发耐受组的外周血中CD4+CD25+Treg比例均增加,术后10 d耐受组CD4+CD25+Treg比例明显高于同基因组(P<0.01)。术后30 d,耐受组CD4+CD25+Treg比例仍维持在较高水平。结论 BN与LEW大鼠组合可建立稳定可靠的急性排斥模型与自发耐受模型。CD4+CD25+Treg可能参与自发免疫耐受的形成。     

CD28/B7和CD134/CD134L共刺激通路阻断与免疫抑制剂联合治疗对移植心脏存活时间影响

目的探讨CD28-B7、CD134-CD134L共刺激信号通路阻断以及雷帕霉素、供体特异性脾细胞输注(DST)等联合治疗对心脏移植排斥反应的影响。方法将DA大鼠心脏移植到LEW大鼠的腹腔内,用CTLA4-Ig融合蛋白、CD134L抗体分别阻断CD28-B7、CD134-CD134L共刺激信号通路,以及雷帕霉素、DST等不同治疗组合观察对移植心脏存活时间的影响,并利用免疫组化方法观察炎症细胞浸润情况。结果CD134-CD134L、CD28-B7共刺激信号通路单独阻断和雷帕霉素单独治疗后心脏存活时间分别为7.6+0.5d、12+3.5d和19.1+6d;CD134-CD134L、CD28-B7共刺激信号通路阻断与雷帕霉素联合治疗心脏存活时间分别为25.2+2.2d和31.5+4.6d。CD134-CD134L、CD28-B7共刺激信号通路共同阻断与雷帕霉素、DST联合治疗心脏存活时间明显延长,为59.1±10.4d,另外有2例存活时间超过120d。结论单独雷帕霉素、CD134-CD134L和CD28-B7通路阻断对移植心脏炎症细胞浸润和组织坏死程度无明显改善,而两个共刺激通路同时阻断与雷帕霉素、DST联合治疗时改善效果最明显。     

肝移植自发免疫耐受大鼠CD8+CD28-T抑制细胞的生物学特性

目的　研究近交系大鼠原位肝移植自发免疫耐受模型中CD8 CD2 8- T抑制细胞的生物学特点。方法　建立大鼠原位肝移植模型 ,流式细胞技术检测自发免疫耐受模型中CD8 CD2 8- T抑制细胞含量变化 ;通过体外混合淋巴细胞反应和体内输注验证CD8 CD2 8- T细胞的抑制功能 ,并检测其增殖、细胞因子mRNA的表达和诱导靶细胞发生凋亡的情况 ,并与急性排异组相比较。结果　自发免疫耐受模型大鼠脾脏CD8 CD2 8- T细胞含量 (31.5 %± 2 .6 % )显著高于正常大鼠 (5 .4 %±1.5 % )和急性排异组大鼠 (6 .0 %± 1.3% )。自发免疫耐受组CD8 CD2 8- T细胞明显抑制体外混合淋巴细胞反应的增殖 ,体内输注显著延长皮肤移植物的存活时间 (MST :10± 0 .8dvs 15± 1.8d ,P <0 .0 5 ) ,但急性排异组大鼠脾脏CD8 CD2 8- T细胞无抑制功能。外源性IL 2 4 0U ml可逆转CD8 CD2 8- T细胞的抑制功能。CD8 CD2 8- T细胞不会增加靶细胞凋亡的发生 ,其IFN γmRNA为高表达 ,而急性排异组无表达。PHA 5 0 μg ml和IL 2 4 0U ml、PMA ion 5 0 2 5 0ng ml和IL 2 4 0U ml联合应用可有效刺激CD8 CD2 8- T细胞增殖。结论　自发耐受组大鼠脾脏CD8 CD2 8- T细胞是一种T抑制细胞 ,在自发免疫耐受的形成过程中具有重要作用 ,其抑制作用可能与IFN     

供体凋亡淋巴细胞预输注对猪肝移植受体CD4+T、CD8+T、CD4+CD25+调节性T细胞的影响

背景：凋亡细胞能够主动调节机体的免疫功能,并能通过调节机体细胞免疫和体液免疫的途径诱导免疫耐受,但这些结果只在大鼠肝脏移植模型中证实。 目的：探讨通过⁶⁰Co γ射线体外处理后的供体淋巴细胞预输注诱导猪肝移植特异性免疫耐受的作用中,对淋巴细胞亚群的影响。 方法：建立非转流小型猪原位肝移植模型。将受体猪随机摸球法均分为2组：空白对照组,受体猪无特殊处理,行肝移植;淋巴细胞组：受体猪在肝移植前7 d经耳静脉注射⁶⁰Co γ射线处理过的5×10⁸个供体淋巴细胞。观察两组受体猪移植后的存活时间,移植后T淋巴细胞亚型CD4⁺T、CD8⁺T、CD4⁺CD25⁺Tr变化及病理。 结果与结论：移植后3 d,两组病理活检均呈急性中、重度排斥反应;移植后6 d,两组均呈急性重度排斥反应。移植后1,3,6 d CD4⁺T、CD8⁺T、CD4⁺CD25⁺Tr升降趋势,两组间差异无显著意义(P > 0.05)。提示,⁶⁰Co γ射线体外处理过的淋巴细胞预输注未能够诱导猪同种异体肝移植特异性免疫耐受,未能引起T淋巴细胞亚群变化有关。     

CFSE标记抗原特异性CD4+CD25+T细胞在胰岛移植体内归巢的研究

目的:观察抗原特异性CD4 CD25 Treg细胞在小鼠同种异体胰岛移植后体内的分布特点,探讨抗原特异性CD4 CD25 Treg细胞免疫调节可能机制。方法:构建小鼠同种异体胰岛移植模型。CFSE对抗原特异性CD4 CD25 Treg细胞标记,经尾静脉输注。用组织冰冻切片和流式细胞术动态了解CFSE标记的抗原特异性CD4 CD25 Treg细胞在受体内的分布和增殖变化。结果:抗原特异性CD4 CD25 Treg细胞联合胰岛移植组胰岛移植物平均生存期为(34.57±17.15)d,较胰岛移植组生存时间(10.6±1.82)d,差异有统计学意义(P<0.01)。抗原特异性CD4 CD25 Treg细胞在各级淋巴结均有能定居,但是胰腺淋巴结定居的细胞数量明显多于其他淋巴结。结论:抗原特异性Treg细胞抑制STZ诱导的糖尿病小鼠的急性移植排斥反应,细胞抑制功能与细胞在体内淋巴结的归巢有关。     

天花粉蛋白合成肽通过诱导CD8抑制性T细胞治疗实验性自身反应性脑脊髓炎

为了探讨天花粉蛋白合成肽(M-Tk)治疗实验性自身反应性脑脊髓炎(EAE)的可能性及其作用机制,应用自身抗原MBP衍生肽MOG35-55免疫C57BL/6小鼠成功地诱发EAE后,以流式细胞术测定小鼠淋巴结细胞及脾细胞T亚群及细胞因子的表达,并通过临床评分观察M-Tk治疗EAE的有效性,包括以HE和LFB染色观察髓鞘病变。结果发现,M-Tk可抑制MOG35-55特异性T细胞的增殖反应,选择性诱导CD8+CD28-T调节细胞的扩增,明显提高IL-10的分泌和降低IFN-γ的产生,并有效改善EAE小鼠神经功能评分。采用M-Tk诱导的CD8 T细胞作体内输注可取得相似甚至更好的治疗效果(P>0.01)。提示M-Tk在体内诱导产生CD8+CD28-抑制性T细胞并上调IL-10分泌降低IFN-γ产生,是对EAE取得疗效的关键。     

调节性T细胞在大鼠小肠移植急性排斥反应中的作用

目的 分析调节性T细胞在大鼠急性排斥反应中的作用。方法 采用免疫组化SABC染色法，测定BN→LEW大鼠小肠移植急性排斥反应时，外周血及移植肠浸润淋巴细胞中调节性T细胞：CD4^ ,CD8^ ,CD25^ T淋巴细胞及相关细胞因子IL－4和IFN－γ的表达，并与同基因大鼠间小肠移植（BN→BN）作比较。结果 外周血淋巴细胞分析显示，大鼠小肠移植急性排斥反应时，以CD4^ ,CD25^ ,T细胞为主，CD8^ 淋巴细胞只占少部分；分泌IL－4的细胞在术后4，7，14d分别只占14．3％，16．2％和16．9％。移植肠基底浸润的淋巴细胞以CD4^ ,CD25^＋和分泌IFN－γ的淋巴细胞为主。结论 在大鼠同种小肠移植中，急性排斥反应与CD25^ ,CD4^ T细胞及Th1相关细胞因子IFN－γ的表达增加相关。而CD8^＋T淋巴细胞和Th2相关细胞因子IL－4可能具有保护作用。     

T细胞疫苗免疫前后外周血CD4~ 和CD8~ T细胞变化的分析

目的 观察T细胞疫苗免疫前后外周血CD4~+和CD8~+T细胞的变化情况,探讨T细胞疫苗诱导特异性免疫耐受的作用及其机理。方法 制备针对Wistar大鼠的SD大鼠T细胞疫苗,用制备好的T细胞疫苗去免疫正常的SD大鼠,同时设特异性抗原对照组和空白对照组。于免疫前和免疫后规定时点分别进行单向混合淋巴细胞反应(MTT法),于相同时点通过流式细胞分析对外周血CD4~+和CD8~+T细胞进行检测。结果 在T细胞疫苗组,平均OD值免疫后比免疫前显著降低(P<0.01)CD4/CD8比值免疫后比免疫前显著降低(P<0.05);在特异性抗原对照组,免疫后的OD值显著高于免疫前(P<0.01),同时CD4/CD8比值于免疫后显著增高(P<0.05);空白对照组各时点各指标比较无显著差异(P>0.05)。结论T细胞疫苗可以诱导同种抗原特异性免疫耐受,CD4~+反应性T细胞克隆与CD8~+抗独特型T细胞克隆相对比例优势的转换可能在T细胞疫苗诱导的免疫耐受形成中发挥关键作用。     

阻断型CD154抗体和CD80抗体生物学作用的研究

为比较阻断型抗人CD154单克隆抗体(1B1)和抗人CD80单克隆抗体(3H8)的单独及联合应用在调节CD4+T细胞对同种抗原的初次和再次免疫应答中的作用。采用免疫磁珠阴性选择法分离获得人外周血CD4+T细胞、将纯化的CD4+T细胞与刺激细胞体外共培养,通过检测培养上清IL-2、IFN-γ水平以及CD4+T细胞的增殖来评价1B1和3H8的生物学作用。结果显示,1B1和3H8单独或联合应用能不同程度地抑制混合淋巴细胞反应中CD4+T细胞对同种抗原刺激的增殖,下调CD4+T细胞分泌IL-2和IFN-γ,并且在再次反应中能有效诱导CD4+T细胞对同种抗原的免疫低反应性。因此,1B1和3H8的单独及联合应用在移植排斥的免疫干预及同种抗原免疫耐受的诱导中具有潜在的应用前景。     

供体抗原特异性的CD4~+CD25~+Treg对肾移植大鼠体内B细胞功能的影响

目的 供体抗原特异性的CD4+CD25+Treg体内应用后对同种异系肾移植大鼠受体B细胞功能的影响.方法 以F344大鼠为供体、Lewis大鼠为受体建市大鼠肾移植模型,于术前1大、术后2周分别将供体抗原特异性的CD4+CD25+Treg(1×106)于尾静脉注入受休体内,术后1月抽取人鼠外周血,分离B细胞,检测其在抗IgM抗体刺激下的增殖情况,检测大鼠外周血IgG、IgA水平,以判断应用CD4+CD25+Treg后大鼠体内B细胞功能状态.实验分组:实验组术前、术后2周使用CD4+CD25+Freg(n=8),阳性对照组术前、术后未使用CD4+CD25+Treg(n=8),空白对照组未移植大鼠(n=8).结果 实验证实实验组B细胞增殖水平最低、空白对照组其次,阳件对照组最高,三者均有显著差异(P＜0.05),外周血IgG、lgA水平检测证实,实验组与空的对照组无显著差异(P＞0.05),二者明显低于阳性对照组(P＜0.01).结论 经尾静脉注入CD4+CD25+Treg后肾移植受体体内B细胞的功能可明显受到抑制,CD4+CD25+Treg 可通过对B细胞的这一作用调节受体免疫状态,从而达到控制排斥反应,诱导免疫耐受的作用.     

A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation

INTRODUCTION: The relative contributions of CD4+ and CD8+ T cells to transplant rejection remain unknown. The authors integrated a previous model of CD4-mediated graft rejection with a complementary model of CD8-mediated rejection to directly compare the function of graft-reactive CD4+ and CD8+ lymphocytes in vivo in a model where rejection requires transgenic T cells. These studies allow direct comparison of CD4 and CD8 T cell responses to the same antigen without the confounding effects of T cell depletion or homeostatic proliferation. MATERIALS AND METHODS: Clone 4 and TS1 mice possess MHC class I- and II-restricted CD8+ and CD4+ T cells, respectively, which express transgenic T cell receptors that recognize the influenza hemagglutinin antigen (HA). We compared the in vivo response of CFSE-labeled, HA-specific transgenic CD8+ and CD4+ T cells after adoptive transfer into syngeneic BALB/c mice grafted with HA-expressing skin. RESULTS: As in the authors' CD4+ model, HA104 skin was consistently rejected by both Clone 4 mice (n=9, MST: 14.2) and by 5 x 10(5) Clone 4 lymphocytes transferred to naive BALB/c hosts that do not otherwise reject HA+ grafts. Rejection correlated with extensive proliferation of either graft-reactive T cell subset in the draining lymph nodes, and antigen-specific CD4+ and CD8+ cells acquired effector function and proliferated with similar kinetics. CONCLUSIONS: These data extend the authors' unique transgenic transplantation model to the investigation of CD8 T cell function. The initial results confirm fundamental functional similarity between the CD4 and CD8 T cell subsets and provide insight into the considerable redundancy underlying T cell mechanisms mediating allograft rejection.     

Persisting alloantigen prevents primed CD45RC- CD4 T cells from inducing allograft rejection: implications for immunological memory.

Antigen stimulation induces specific CD4 T cells to change from a resting phenotype (CD45RC+) to a "memory" phenotype (CD45RC-), an isoform switch that is reversible and regulated by persisting antigen. We show here that CD4 T cells responsible for mediating allograft rejection undergo a similar CD45RC+ to CD45RC- switch irrespective of whether antigen priming results in sensitization or tolerance in vivo. Thus, skin allograft priming, designed to induce second set rejection, and a donor-specific blood transfusion (DST), designed to prolong cardiac allograft survival, will generate CD45RC- CD4 T cells that induce acute rejection when adoptively transferred to T cell-deficient athymic nude recipients. The ability of CD45RC- T cells, obtained from DST donors, to induce graft rejection was prevented by giving nude recipients a DST 14, 28 or even 56 days before grafting and T cell transfer. Thus, prolonged allograft survival in rats after DST was found to be strongly linked with persisting alloantigen from the blood transfusion but was not associated with detectable microchimerism. Importantly, CD45RC- T cells from skin graft-primed animals were similarly prevented from inducing rejection by residual DST-derived alloantigen. The investigation shows (1) that an allogeneic blood transfusion primes (not tolerizes) alloreactive CD4 T cells and (2) that residual DST-derived alloantigen can block the action of specifically primed "memory" CD4 T cells. These findings have implications for understanding immunological memory.     

B cells can prime naive CD4+ T cells in vivo in the absence of other professional antigen-presenting cells in a CD154-CD40-dependent manner

The role of B cells as APC is well established. However, their ability to prime naive T cells in vivo has been difficult to examine because of the presence of dendritic cells. The current studies were undertaken to examine this issue in a model of adoptive transfer of antigen-specific B cells and T cells into histoincompatible Rag2(-/-) mice. By means of this system, we were able to demonstrate that antigen-specific B cells are competent APC for naive CD4(+) T cells specific for the same antigen. In vivo antigen presentation resulted in expansion of both CD4(+) T cells and B cells. The antigen-presenting function of the transferred B cells was dependent on the CD154-CD40 interaction, as transfer of CD154-deficient antigen-specific CD4(+) T cells or CD40-deficient B cells failed to induce T and B cell expansion in response to immunization. These results indicate that antigen-specific B cells have the capacity to induce primary T cell responses in the absence of other competent APC.     

Low-avidity CD8lo T cells induced by incomplete antigen stimulation in vivo regulate naive higher avidity CD8hi T cell responses to the same antigen

We have previously reported that multiple injections of soluble MHC class I tetramers assembled with wild-type HY peptide induces unresponsiveness to male skin grafts in naive female C57BL/6 (B6) mice. Induction of unresponsiveness is dependent on a population of unresponsive allospecific CD8(lo )T cells. Reduced expression of CD8 acts to limit a T cell response to HY peptide by limiting the avidity window of effective signal transduction. We and others have demonstrated that CD8(lo) T cells are an alternative stable phenotype of CD8alphabeta(+) T cells in vitro and in vivo after antigen stimulation. We show here that CD8(lo) T cells can suppress naive CD8(+) T cell responses to HY antigen in vitro and male skin graft rejection in vivo after adoptive transfer into female recipients. These novel regulatory T cells express surface TGF-beta1 and secrete T cytotoxic 2 cytokines after antigen-specific stimulation. Anti-TGF-beta antibody and latency-associated peptide inhibit the suppressive effects in vitro. We also show that HY-specific memory CD8(+) T cells overcome regulation by CD8(lo) T cells. These data define a novel peripheral regulatory CD8(+ )T cell population that arises after repeated antigen encounter in vivo. These cells have implications in the maintenance of tolerance and memory.     

A model of suppression of the antigen-specific CD4 T cell response by regulatory CD25+CD4 T cells in vivo

Despite intense recent interest, the suppressive mechanisms of regulatory CD25+CD4 T cells remain poorly understood. One deficiency in the field is the lack of in vivo models where the effects of regulatory CD25+CD4 T cells on antigen-specific responder T cells can be measured quantitatively. We describe one such model here. We compared responses of adoptively transferred naive wild-type antigen-specific CD4 T cells in syngeneic CD28-/- and wild-type recipient mice toward a nominal antigen. The cells exhibited a greater degree of proliferation and differentiation in CD28-/- mice and could not be rendered functionally hyporesponsive by systemic exposure to adjuvant-free antigen. The only reason we were able to find to explain this difference was the deficiency of regulatory CD25+CD4 T cells in the CD28-/- mice. Use of CD28-/- mice as adoptive transfer recipients provides a simple model that reveals the contribution of regulatory CD25+CD4 T cells in controlling antigen-driven responses in vivo.     

Role of CD8alpha+ and CD8alpha- dendritic cells in the induction of primary immune responses in vivo.

Data from adoptive transfer of mature dendritic cells (DC) indicate that they are responsible for the induction of primary immunity. Two subclasses of DC have been recently identified in spleen that differ in their phenotype and in certain regulatory features. In vitro, both subsets have the capacity to activate naive T cells, although CD8a+ DC have been shown to induce T cell apoptosis and to stimulate lower levels of cytokines compared with CD8alpha- DC. The objective of this study was to analyze the function of these distinct DC types in vivo. Our results show that both subsets, pulsed extracorporeally with antigen and injected in the footpads of syngeneic mice, sensitize an antigen-specific T cell primary response. However, CD8alpha+ cells trigger the development of Thl-type cells, whereas CD8alpha- DC induce a Th2-type response. These observations suggest that the Th1/Th2 balance in vivo is regulated by the antigen-presenting-cells of the primary immune responses.     

Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance

After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross-presented on H-2K(b) by LSEC to naive CD8 T cells. Cross-presentation efficiency in LSEC but not dendritic cells was increased by antigen-exposure to heat or low pH. Mechanistically, cross-presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H-2K(b)-restricted cross-presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2-/- knockout mice, previously reconstituted with naive ovalbumin-specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN-gamma in CD8 T cells. Using a new transgenic mouse line expressing H-2K(b) only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H-2K(b)-restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens.     

CD8+ alphabeta T cells can mediate late airway responses and airway eosinophilia in rats

BACKGROUND: The function of CD8+ T-cell subsets in mediating late allergic responses is incompletely understood. OBJECTIVE: We sought to test the hypothesis that CD8+ alphabeta T cells are proinflammatory in the airways in vivo by using a well-characterized animal model and the technique of adoptive transfer. METHODS: Brown Norway rats were administered CD8 + alphabeta T cells (10 6 ) intraperitoneally purified from lymph node cells of either naive or ovalbumin (OVA)-sensitized rats and were challenged with aerosolized OVA 2 days later. Control rats were sensitized to 100 mug of OVA in Al(OH) 3 subcutaneously or sham sensitized to saline and were OVA challenged 2 weeks later. RESULTS: The OVA-sensitized and OVA-challenged group and the recipients of OVA-primed CD8+ alphabeta T cells had significant late airway responses calculated from lung resistance measured for an 8-hour period after challenge compared with the naive CD8 + alphabeta T cell-transferred group and the sham-sensitized control group. The number of eosinophils in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with numbers in the naive CD8+ alphabeta T-cell recipients and the sham-sensitized control group. IL-4 and IL-5 cytokine mRNA expression in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with that in the sham-sensitized group. CONCLUSION: We conclude that antigen-primed CD8 + alphabeta T cells might have a proinflammatory role in allergen-driven airway responses in the rat.     

CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model

CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.     

The role of CD4+ T-cell subsets in determining transplantation rejection or tolerance

Summary: Peripheral tolerance to allogeneic organ grafts can be induced in rodents by treating with non-depleting CD4 and CD8 monoclonal antibodies. This tolerance is maintained by CD4⁺ T cells with a potent capacity to induce tolerance in further cohorts of T cells (i.e. infectious tolerance). We have cloned CD4⁺ T-cell subsets against the male transplantation antigen in vitro and find, in contrast to Th1 or Th2 clones that elicit rejection, that there is a distinct population of CD4⁺ T cells that suppress rejection by adoptive transfer (here called T reg ). In order to identify molecular markers associated with tolerance and gain insights into the mechanisms of action of T reg cells, we carried out serial analysis of gene expression. We identified genes overexpressed in T reg compared to Th1 and Th2 cultures and found that some of these correlated in vivo with CD4-induced transplantation tolerance rather than rejection. The genes overexpressed in T reg cultures and within tolerated skin grafts were primarily expressed by mast cells (e.g. tryptophan hydroxylase and FcεR1α), suggesting that regulatory cell activity and this form of tolerance may be associated with a localised but non-destructive form of Th2-like activation and a recruitment of mast cells.