Effect of Ionizing Radiation on the Expression of p16, CyclinDI and CDK4 in Mouse Thymocytes and Splenocytes

Objective To investigate the effect of ionizing radiation on the expression of p16, CyclinDl, and CDK4 in mouse thymocytes and splenocytes. Methods Fluorescent staining and flow cytometry analysis were employed for the measurement of protein expression. Results In time course experiments, it was found that the expression of p16 protein was significantly increased at 8, 24, and 48 h for thymocytes (P<0.05, P<0.01, and P<0.05, respectively) and at 24 h for splenocytes (P<0.05) after whole body irradiation (WBI) with 2.0 Gy X-rays. However, the expression of CDK4 protein was significantly decreased from 8 h to 24 h for thymocytes (P<0.05,P<0.01) and from 8 h to 72 h for splenocytes (P<0.05-P<0.01). In dose effect experiments, it was found that the expression of p16 protein in thymocytes and splenocytes was significantly increased at 24 h after WBI with 1.0, 2.0, and 4.0 Gy (P<0.05-P<0.01), whereas the expression of CDK4 protein was significantly decreased with 2.0Gy for thymocytes (P<0.05) and 0.5-6.0 Gy for splenocytes (P<0.05-P<0.01). Results also showed that the expression of CyclinDl protein decreased markedly in both thymocytes and splenocytes after exposure. Conclusion The results indicate that the expression of p 16 protein in thymocytes and splenocytes can be induced by ionizing radiation, and the p16-CyclinD1/CDK4 pathway may play an important role for G1 arrest of thymocytes induced by X-rays.

Clusterin mRNA expression in apoptotic and activated rat thymocytes

Clusterin is a 75-80 kDa heterodimeric glycoprotein, that is produced in most tissues but which exactbiological role is still not clear. Particularly, its role in protection or promotion of apoptosis is heavilydisputed, since data supporting both views have been reported in several independent studies. To clarify thisissue, and also to determine whether clusterin expression itself might be affected by apoptosis, in the presentstudy, rat thymocytes were treated with dexamethasone, -a synthetic glucocorticoid that elicits apoptosis inthymocytes-, and clusterin mRNA expression was analyzed by semi-quantitative RT-PCR before and afterinduction of apoptosis. Interestingly, neither the treatment with dexamethasone in vitro nor triggering ofapoptosis in vivo up- regulated clusterin expression, opposing the view that clusterin is involved in apoptoticprocesses. On the other hand, a new clusterin mRNA isoform was detected and isolated, whose expressionwas restricted to freshly isolated thymocytes. This novel isoform lacks the post-translational proteolyticcleavage site and is therefore predicted to encode a monomeric protein. The biological function undernormal circumstances, however, will need further investigations for clarification. While apoptosis could notmodulate clusterin expression, activation of thymocytes with concanavalin A and interleukin-2 resulted inup-regulation of clusterin mRNA level, indicating that clusterin expression is rather under the control ofcell activation-mediated rather than apoptosis- induced signals.

c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2

T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for posi- tive selection is survival. TCR signal-induced Bcl-2 expression is believed to play a dominant role in the survival of positively selecting thymocytes, but how Bcl-2 is directly regulated is unknown. Here we report that the immediate early gene （IEG） c-Fos can stimulate the expression of Bcl-2, depending on a specific AP-l-binding site in the Bcl-2 promoter. In c-Fos transgenic （Fos-Tg） mice, c-Fos binds to this site and promotes the expression of Bcl-2. As a result, Fos-Tg thymocytes exhibited enhanced survival, and more mature single-positive （SP） thymocytes were generated, even on a unique TCR background. The TCR repertoire remained normal in Fos-Tg mice. Our results identified c-Fos as the mediator of the stimulatory effect of TCR signaling on Bcl-2 expression. Therefore, c-Fos, as an IEG, because of its early response ability, can quickly rescue the survival of short-lived thymocytes during positive selection. Our results provide novel insight into the mechanism regulating the survival of positively selecting thymocytes.

Effects of an immunosuppressive active component of Periplocae Cortex (Periploca sepium Bge.) on positive selection of thymocytes in vitro

Objective:To determine the effect of an immunosuppressive active component (periploside A) isolated from the stem bark of Periplocae Cortex (Periploca sepium Bge.),a Chinese medicinal herb used in the treatment of rheumatoid arthritis for centuries in China,on positive selection of thymocytes in vitro.Methods:Female C57BL/6 mice at 6 weeks of age were housed in specific pathogen-free conditions.Double-positive thymocytes from C57BL/6 mice were induced into positive selection in vitro with or without periploside A treatment.Cell viability and expression of CD69,CD4,and CD8 were analyzed by flow cytometry.Results:Flow cytometric examination of thymocyte populations revealed that the percentage of CD8+ single-positive thymocytes was decreased by periploside A upon differentiation induced by an anti-CD3 antibody.However,the percentage of CD4+ single-positive thymocytes was decreased by periploside A upon differentiation induced by phorbol 12-myristate 13-acetate/ionomycin.Expression of CD69 plays a major role in prohibiting differentiation of thymocytes.Treatment with periploside A decreased CD69 expression in thymocytes.Conclusion:These results demonstrate that periploside A influences positive selection of thymocytes in vitro.

X-ray irradiation selectively kills thymocytes of different stages and impairs the maturation of donor-derived CD4^+CD8^+ thymocytes in recipient thymus

The aim of the present study was to determine whether the sensitivity of thymocytes to X-ray radiation depends on their proliferative states and whether radiation impairs the maturation of donor-derived thymocytes in recipient thymus.We assigned 8-week-old C57BL/6J mice into three treatment groups：1） untreated;2） X-ray radiation;3） X-ray radiation plus bone marrow transplantation with donor bone marrow cells from transgenic mice express-ing enhanced green fluorescent protein（GFP） on a universal promoter.After 4 weeks,the size of the thymus,the number and proliferation of thymocytes and ratios of different stage thymocytes were analyzed by immunohisto-chemistry and flow cytometry.The results showed that：1） CD4＋CD8＋ thymocytes were more sensitive to X-ray radiation-induced cell death than other thymocytes;2） the proliferative capacity of CD4＋CD8＋ thymocytes was higher than that of other thymocytes;3） the size of the thymus,the number of thymocytes and ratios of thymo-cytes of different stages in irradiated mice recovered to the normal level of untreated mice by bone marrow trans-plantation;4） the ratio of GFP-positive CD4＋CD8＋ thymocytes increased significantly,whereas the ratio of GFP-positive CD4＋ or CD8＋ thymocytes decreased significantly.These results indicate that the degree of sensitivity of thymocytes to X-ray radiation depends on their proliferative states and radiation impairs the maturation of donor-derived CD4＋CD8＋ thymocytes in recipient thymus.

Selective support of a mouse thymus epithelial cell line（MTEC1）to the viability and proliferation of CD4^+CD8^-,CD4^-CD8^-,and CD4^+CD8^+thymocytes in vitro

The MTEC1 cell line, established in our laboratory, is a normal epithelial cell line derived from thymus medulla of Balb/c mice and these cells constitutively produce multiple cytokines. The selection of thymic microenvironment on developing T cells was investigated in an in vitro system. Un-separated fresh thymocytes from Balb/c mice were cocul-tured with MTECl cells or/and MTEC1-SN,then,the viability, proliferation and phenotypes of cultured thymocytes were assessed. Without any exogenous stimulus, both MTECl cells and MTECl -SN were able to maintain the viability of thymocytes, while only the MTECl cells, not the MTECl -SN, could directly activate thymocytes to exhibit moderate proliferation, indicating that the proliferative signal is delivered through cell surface interactions of MTECl cells and thymocytes. Phenotype analysis on FACS of viable thymocytes after coculture revealed that MTECl cells preferentially activate the subsets of CD4+ CDS', CD4+ CD8+ and CD4- CD8- thymocytes; whereas MTEC1- SN preferentially maintained the viability of CD4+ CD8- and CD4-CD8+ thymocyte subsets.For the Con A-activated thymocytes, both MTEC1 cells and MTEC1-SN provided accessory signal(s) to significantly increase the number of viable cells and to markedly enhance the proliferation of thymocytes with virtually equal potency, phenotyped as CD4+CD8-, CD4-CD8+, and CD4- CD8- subsets. In summary, MTEC1 cells displayedselective support to the different thymocyte subsets , and the selectivity is dependent on the status of thymocytes.

RESPONSES OF HUMAN FETAL SPLENOCYTES AND THYMOCYTES TO INTERLEUKIN-2: LAK ACTIVITY AND PROLIFERATION

Using cytotoxicity and thymidine uptake assays, we investigated the effects of human recombinant in-terleukin-2 (rIL-2) on the induction of lympholine-activated killer (LAK) activity and cellular proliferation in splenocytes and thymocytes from human fetuses (18-22 weeks). We observed that fetal splenocytes and thymocytes incubated with low doses of rIL-2 (10-100 U ml) developed broad antitumor activity (LAK activity) although the kinetics and magnitudes of the responses were different. It indicated the LAK precursors are present in fetal spleen and thymus. Further, rIL-2 induced a strong proliferative response in splenocytes, but not in thymocytes. On the basis of the findings, we conclude that the responses of fetal splenocytes and thymocytes to IL-2 are different.

风险管理对再生障碍性贫血ATG治疗期间不良事件的应用效果分析

目的:观察风险管理在再生障碍性贫血患者接受免抗人胸腺细胞免疫球蛋白(ATG)治疗期间对不良事件的防治效果。方法:选取2020年8月—2022年3月南阳医学高等专科学校第一附属医院接受ATG治疗的127例再生障碍性贫血患者作为研究对象,采用电脑随机分组法将其分为干预组(64例,实施基于风险管理的临床护理)和常规组(63例,仅实施临床基础护理)。比较两组患者治疗期间不良事件发生情况、症状改善情况及预后情况。结果:干预组患者不良事件发生率低于对照组,差异有统计学意义(χ^(2)=5.433,P<0.05);干预组患者T淋巴细胞亚群与对照组比较,差异有统计学意义(t=9.832、10.197、28.313、3.712,P<0.05);干预组患者血红蛋白(Hb)、红细胞计数(RBC)、血小板计数(PLT)、中性粒细胞百分比(NE)高于对照组,差异有统计学意义(t=2.345、14.917、16.204、12.200,P<0.05);干预组患者随访期间病情复发率、死亡率低于对照组,简明健康生活状况量表(SF-36)评分高于对照组,差异有统计学意义(χ^(2)=7.832、7.685,t=11.386,P<0.05)。结论:在再生障碍性贫血患者接受ATG治疗期间实施风险管理对降低不良事件发生率、增强治疗效果、改善免疫功能及预后并提升生活质量均有积极意义。

Effect of bilateral testicular resection on thymocyte and its microenvironment in aged mice

Aim: To observe the changes in thymocyte and its microenvironment in aged mice after bilateral testicular resection.Methods: In male old mice, at the 25th day after testicular resection, the peripheral blood and thymus were collect-ed . Blood and thymus suspension smears were prepared for quantitative histochemistry and immunohistochemistry studyunder light and electron microscopes. Results; In testes resected mice the size and the weight of thymus weremarkedly increased. The demarcation between cortex and medulla was clear. The cortex was thickened and the celldensity was increased. The ratio of cortex/medulla stereometry was increased. The total cell count, thymocyte count,the percentage of acid a-naphthyl acetate esterase (ANAE) positive thymocytes, nonlymphocytes and the rosette forma-tion of macrophages and thymocytes were all increased. The thymocytes surrounded closely to the light thymic epithelialcells, dendritic cells or macrophages. The lymphocytes, particularly the ANAE positive lymphocytes of peripheralblood were increased. Conclusion; After bilateral testicular resection, the thymus of aged male mice showed mor-phological regeneration and the thymocytes and its microenvironment appeared to be definitely improved. It is suggestedthat testicular resection may improve immune function. (Asian J Androl 2001 Dec; 3; 271 — 275)

The serine/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression

LKB1 is a serine/threonine kinase that directly activates the energy sensor AMP-activated protein kinase （AMPK） in response to bioenergetic stress, and mainly acts as a tumor suppressor that controls cell polarity and proliferation. Although LKB1 is expressed in multiple tissues including the thymus and the spleen, its roles in T-cell development and function remain unknown. Here, we show that T-cell-specific deletion of LKB1 resulted in reduced survival of double-positive （DP） thymocytes and impaired generation of both CD4 and CD8 single-positive thymocytes. Disruption of LKB1 not only prevented the activation of AMPK but also impaired the expression of anti-apoptotic protein BcI-XL. Importantly, ectopic expression of either BcI-XL or the constitutively active AMPK mutant significantly rescued DP thymocytes from LKB1 deficiency-induced cell death. Moreover, ectopic expression of the constitutively active AMPK mutant was found to restore the expression of BcI-XL in LKB1-deficient DP thymocytes. These findings identify LKB1 as a critical factor for the survival of DP thymocytes through regulation of AMPK activation and Bcl-XL expression.

Time-effect of adaptive response of mouse thymocyte apoptosis and cell cycle progression induced by low dose radiation

目的 :观察低剂量辐射 (LDR)诱导胸腺细胞凋亡及细胞周期进程适应性反应的基本规律。方法 :用 X射线照射昆明系雄性小鼠 ,其诱导剂量 (D1)及其后攻击剂量 (D2 )分别是 75m Gy和 1.5Gy。D1和 D2 间隔时间分别是 3、6、12、2 4和 6 0 h。D2 照射后 18h胸腺细胞培养 4、2 0和 4 4 h用流式细胞仪检测胸腺细胞凋亡小体 (TAB)和细胞周期进程的变化。结果 :当 D1和 D2 间隔 3、6和 12 h,在 D2 照射后胸腺细胞培养 4和 2 0 h,D1+ D2 组 TAB百分数明显低于 D2 组 (P<0 .0 5) ,G0 / G1和 G2 + M期细胞百分数也不同程度地低于 D2 组 ,而 S期细胞百分数却明显高于 D2 组 (P<0 .0 5或 P<0 .0 1)。结论 :D1和D2 分别是 75m Gy(剂量率 ,12 .5m Gy/ min)和 1.5Gy(剂量率 ,0 .2 87Gy/ min) ,D1和 D2 间隔 3～ 12 h,在小鼠全身照射后其胸腺细胞培养 4和 2 0 h可诱导细胞凋亡和细胞周期进程的适应性反应。

Studies on Proliferationpromoting Effect of Supernatant from Human Thymic Epithelial Cell Culture on Mouse Thymocyte and Tcell Line

Supernatants from human primary thymic epithelial cell culture were collected. The proliferationpromoting effect of the supernatant on mouse thymocyte, as well as on Tcell line 85, Be 13, HDMar, Peer, Loucy, Molt4, Reh and Jurkat, were observed. The results demonstrated that the supernatants could increase spontaneous 3 HTdR intake of mouse thymocyte, promote ConAinduced thymocyte proliferation and stimulate the proliferation of 85 cell or the cells of HDMar, Loucy and Jurkat at stationary phase, but did not display any effect on Be13, Peer, Molt4 and Reh cells.

Kinetics of thymocyte developmental process in fetal and neonatal mice

Kinetics of thymocyte development in vivo during embryogenesis was pursued. The early development of thymocytes in the fetal and neonatal BALB/c mice was discontinuous, with four waves of cell proliferation occurring at fetal day (Fd) 14 to 17, Fd 18 to day (D) 1 after birth, D 2 to D 5 and D6 thereafter. The first three proliferation waves coincided with the generation of CD4/'CD8/' (DP), TCR+CD4/hiCD8-/lo (CD4 SP), and TCR+CD4-/loCD8int/hi (CD8 SP) thymocytes, respectively. The transition from DN to DP cells was further investigated and it was found out that there were two differential pathways via immature single positive (ISP) cells in the BALB/c mice, each functioning at different fetal ages. One is via TCR-CD4-CD8+ cells, occurring between Fd 15 and Fd 17 and the other is via TCR-CD4+CD8- cells, occurring from Fd 17 until birth. In contrast, the TCR-CD4-CD8+ pathway dominated overwhelmingly in the C57BL/6 mice. These findings shed new light on the hypothesis that the differential pathway preference varies with mouse strains. With respect to the shift in the intensity of CD4 and CD8 expression on thymocytes from fetal to adult mice, the TCR+CD4/hiCD8-/lo, and TCR+CD4-/loCD8int/hi subsets might be equivalent to the medullary type TCR+CD4/CD8 SP cells.

The thymic stromal cell line MTSC4 induced thymocyte apoptosis in a non-MHC-restricted manner

Mouse thymic stromal cell line 4 (MTSC4) is one of the stromal cell lines established in our laboratory. While losing the characteristics of epithelial cells, they express some surface markers shared with thymic dendritic cells (TDCs). To further study the biological functions of these cells, we compared the capability of MTSC4 with TDCs in the induction of thymocyte apoptosis, using thymic reaggregation culture system. Apoptosis of thymocytes induced by MTSC4 and TDCs was measured by Annexin V and PI staining and analyzed by flow cytometry. We found that MTSC4 selectively augmented the apoptosis of CD4^+8^+ (DP) thymocytes. This effect was Fas/FasL independent and could not be blocked by antibodies to MHC class Ⅰ and class Ⅱ molecules. In addition, MTSC4 enhanced the apoptosis of DP thymocytes from different strains of mice, which implies that MTSC4-induced thymocyte apoptosis is not mediated by the TCR recognition of self peptide/MHC molecules. In contrast to MTSC4, thymocyte apoptosis induced by TDCs was MHC-restricted. Thus, MHC-independent fashion of stromal-DP thymocyte interaction may be one of the ways to induce thymocyte apoptosis in thymus. Our study has also shown that the interaction of MTSC4 stromal cells and thymocytes is required for the induction of thymocyte apoptosis.

Immunomodulation with rabbit anti-thymocyte globulin in solid organ transplantation

Rabbit anti-thymocyte globulin's manifold mechanisms of action may be attribuited to its polyclonal nature. Its T-cell depleting effect on lymphoid cells is well established: Occurring in the blood and secondary lymphoid tissues, depletion proceeds through complement-dependent lysis, opsonization and apoptotic pathways. Clinical studies have shown that rabbit antithymocyte globulin's immunomodulatory effect extends beyond the initial T-cell depletion and up to the period during which lymphocyte populations begin to recover. The drug is able to mediate immunomodulation and graft tolerance by functionally inactivating cell surface receptors involved in antigen recognition, leukocyte trafficking and leukocyte endothelium adhesion. The complex and prolonged immunomodulation induced by this drug contributes to its efficacy in solid organ transplantation, mainly by reducing the incidence of acute graft rejection.

ABO血型不相容亲属活体肾移植23例报告

目的探讨ABO血型不相容(ABOi)亲属活体肾移植的临床疗效和安全性。方法回顾性分析23例ABOi亲属活体肾移植受者的临床资料。术前根据受者的初始血型抗体滴度,采取不同的个体化预处理方案,包括口服免疫抑制药+利妥昔单抗,或口服免疫抑制药+血浆置换和(或)血浆双重滤过+利妥昔单抗等,监测预处理前、后,肾移植术前及术后的血型抗体滴度和围手术期移植肾功能、相关并发症。并随访移植肾功能及相关并发症。结果23例ABOi亲属活体肾移植受者中,除1例术中出现超急性排斥反应,其余22例血清肌酐水平恢复良好。围手术期并发症包括4例淋巴瘘、1例尿瘘、1例肾周血肿合并T细胞介导的排斥反应、6例泌尿系统感染、1例急性肾小管坏死、1例急性胰腺炎、1例血型抗体反弹、1例原发病复发,经治疗均痊愈。截止至随访日,22例受者的移植物和受者存活率均为100%,移植肾功能良好。随访期间血型抗体滴度均≤1∶8。随访期并发症包括2例严重肺部感染、1例抗体介导的排斥反应、2例原发病复发、1例淋巴囊肿、1例泌尿系统感染、1例带状疱疹、1例BK病毒尿症和2例血糖异常。结论根据不同血型抗体水平选择个体化预处理方案,可以安全地实施ABOi亲体肾移植。但大剂量使用利妥昔单抗,或在高致敏受者中联合使用兔抗人胸腺细胞免疫球蛋白诱导,均可能出现严重的感染并发症。

Dectin-1对侵袭性肺曲霉病大鼠半乳甘露聚糖、胸腺细胞凋亡及肺损伤的影响

目的:探究树突状细胞相关性C型凝集素-1(Dectin-1)对侵袭性肺曲霉病大鼠半乳甘露聚糖(GM)、胸腺细胞凋亡及肺损伤的影响。方法:大鼠随机分为对照组、Ad-EGFP组和Ad-Dectin-1-EGFP组。检测大鼠肺功能(肺容积变换、静息通气量);ELISA法检测大鼠肺泡灌洗液中干扰素γ(IFN-γ)、白细胞介素4(IL-4)含量和血清中GM含量;H-E染色观察肺组织病理学变化;检测胸腺指数;TUNEL检测胸腺细胞凋亡;免疫印迹检测肺组织中Dectin-1、T-bet、GATA-3蛋白表达。结果:与对照组相比,Ad-EGFP组大鼠IFN-γ含量、胸腺指数、肺容积变换和静息通气量均明显降低,IL-4含量、GM值、胸腺细胞凋亡指数明显升高;与Ad-EGFP组相比,Ad-Dectin-1-EGFP组大鼠IFN-γ含量、胸腺指数、肺容积变换和静息通气量均明显升高,IL-4含量、GM值、胸腺细胞凋亡指数明显降低。与对照组相比,Ad-EGFP组大鼠肺组织中Dectin-1、T-bet蛋白表达明显降低,GATA-3蛋白表达明显升高;与Ad-EGFP组相比,Ad-Dectin-1-EGFP组大鼠肺组织中Dectin-1、T-bet蛋白表达明显升高,GATA-3蛋白表达明显降低。结论:Dectin-1重组质粒可减轻侵袭性肺曲霉病大鼠肺损伤,降低血清中GM值,通过抑制胸腺细胞凋亡维持体内免疫功能平衡,其机制可能与T-bet、GATA-3蛋白表达有关。

PLZF调控小鼠早期T细胞发育和自我更新的功能

目的:研究PLZF调控小鼠早期T细胞发育与自我更新的功能,以及PLZF对胸腺细胞发育和自我更新的影响。方法:利用新生小鼠进行胸腺移植,以Rag2/γc−/−小鼠为受体。首先比较PLZF−/−与野生型(PLZF+/+)小鼠胸腺细胞总数的差异,再通过流式细胞术和细胞分选,筛选小鼠的骨髓造血干细胞和胸腺的DN2a细胞以及PLZF−/−小鼠的早期T细胞系前体(ETP),以及PLZF−/−或野生型小鼠在新生小鼠胸腺移植模型的移植物DN1细胞中的表达情况。结果:PLZF−/−小鼠的胸腺细胞总数和早期T细胞系前体数目与野生型小鼠相比显著下降,并且细胞总数的减少不是由细胞内源性引起的。通过研究PLZFEGFP报告基因小鼠和新生小鼠胸腺的肾移植模型,发现PLZF在Rag2/γc−/−受体小鼠胸腺移植物的DN1(Lineage−CD44+CD25−)细胞中高表达,且供体细胞的PLZF缺失会显著影响来源胸腺移植物的DN1细胞的比例。结论:PLZF可能在T细胞的正常增殖发育过程中不是必需的,但很可能参与维持早期T细胞系前体的自我更新。

糖皮质激素诱导大鼠胸腺细胞程序性死亡研究

用甲基强的松龙（ＭＰＳ）与大鼠胸腺细胞共同培养，４ｈ后胸腺细胞超微结构显示胞浆及核固缩，形成大量空泡，而线粒体等细胞器结构变化不大，ＤＮＡ电泳分析有大量小分子片段，分子量为１８０ｂｐ的整倍数，呈梯状结构。结果提示ＭＰＳ可诱导胸腺细胞程序性死亡。

陆皂苷甲对小鼠胸腺细胞凋亡的影响

目的 :研究商陆皂苷甲 (Es A )对小鼠胸腺细胞的凋亡效应的影响。方法 :采用电镜、DNA琼脂糖凝胶电泳和流式细胞仪三种分析方法 ,测定 Es A对小鼠胸腺细胞的凋亡效应的影响。 结果 :Es A在 2 .5～ 10μg/ ml的浓度范围内 ,对小鼠胸腺细胞自发出现的细胞凋亡无影响 ,但能显著地促进 Con A活化的胸腺细胞的凋亡。 结论 :Es A有促进 Con A活化的胸腺细胞凋亡的作用 ,显示商陆皂苷甲对细胞免疫有调节作用。