LFA-1与配体ICAM-1黏附分子功能的研究进展

LFA-1和ICAM-1介导的跨膜双向信号传递在淋巴细胞渗出、活化、黏附、免疫监视、免疫突触形成中都起到重要作用。LFA-1与ICAM-1转导信号依赖于两者之间结合能力的变化。LFA-1对ICAM-1结合能力的调节是一动态过程,LFA-1的亲和力和亲合力变化是两种主要调节方式。LFA-1亚单位的磷酸化、细胞骨架蛋白talin1在LFA-1和ICAM-1信号调节中起重要作用。LFA-1和ICAM-1还可提供协同刺激信号促进淋巴细胞活化、增殖和分化。本文就LFA-1结合能力的调节、LFA-1亚单位的磷酸化调节、talin1在LFA-1和ICAM-1信号转导中的作用、LFA-1与ICAM-1的协同刺激信号进行了综述。     

Intercellular adhesion molecule 3, a third adhesion counter-receptor for lymphocyte function-associated molecule 1 on resting lymphocytes

Recent studies suggest that some T and B lymphocyte cell lines bind to the integrin lymphocyte function-associated molecule 1 (LFA-1) chiefly through a pathway independent of its two known counter-receptors, intercellular adhesion molecules (ICAMs)-1 and -2. A monoclonal antibody (mAb) was raised that, in combination with blocking mAb to ICAM-1 and ICAM-2, can completely inhibit binding of these cell lines to purified LFA-1. This third ligand, designated ICAM-3 based on its functional relatedness to ICAM-1 and -2, is a highly glycosylated protein of 124,000 Mr. It is well expressed on all leukocytes and absent from endothelial cells. In assays of adhesion of resting lymphocytes to purified LFA-1, ICAM-3 is by far the most functionally important ICAM, implying an important role for ICAM-3 in the generation of immune responses.     

Coordinated redistribution of leukocyte LFA-1 and endothelial cell ICAM-1 accompany neutrophil transmigration

The leukocyte integrin lymphocyte function-associated antigen 1 (LFA-1) and its endothelial ligand intercellular adhesion molecule (ICAM)-1 play an important role in transmigration as demonstrated by in vivo and in vitro models of inflammation. Despite the prominent role, little is known concerning the distribution and dynamic behavior of these adhesion molecules during leukocyte transmigration. Therefore, we examined the spatial and temporal distribution of LFA-1 on neutrophils actively transmigrating tumor necrosis factor-alpha-activated human umbilical vein endothelial monolayers under shear flow. Upon neutrophil arrest, LFA-1 was evenly distributed. However, once neutrophils initiated transmigration, LFA-1 rapidly redistributed to form a ringlike cluster at the neutrophil-endothelial junctional interface through which transmigration occurred. As transmigration was completed, LFA-1 redistributed to the neutrophil uropod. Endothelial ICAM-1 and JAM-A both colocalized with the ringlike LFA-1 cluster. Further analysis of PMA-stimulated neutrophils, which increase mobility of LFA-1, showed a rapid redistribution of LFA-1 and ICAM-1, but not endothelial JAM-A. Thus, endothelial JAM-A does not appear to contribute to adhesion or transmigration in this system. This is the first demonstration that neutrophil LFA-1 rapidly redistributes to form a ringlike structure that coclusters with endothelial ICAM-1 as the neutrophil transmigrates.     

Lymphocyte function-associated antigen 1 dominates very late antigen 4 in binding of activated T cells to endothelium

Lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 (LFA-1/ICAM-1)-and very late antigen 4/vascular cell adhesion molecule 1 (VLA-4/VCAM-1)-mediated adhesion of T lymphocytes to endothelial cells (EC) can be regulated by increased expression of ICAM-1 and VCAM-1 upon cytokine treatment of EC, or by activation of the integrin molecules LFA-1 and VLA-4 on T cells. Here, we provide evidence that preferential usage of LFA-1 over VLA-4 is yet another mechanism to control T cell adhesion. We observed that binding of activated T lymphocytes, as opposed to resting T cells, to EC is essentially mediated through LFA-1 and not through VLA-4. VLA-4- mediated adhesion of T cells to EC is only found when LFA-1 is not expressed or not functional, as observed for several T cell leukemia cell lines. These results suggest that LFA-1-mediated adhesion dominates and may downregulate VLA-4-mediated adhesion through an unidentified mechanism.     

Adhesion of human B cells to follicular dendritic cells involves both the lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and very late antigen 4/vascular cell adhesion molecule 1 pathways

Presentation of antigen in the form of immune complexes to B lymphocytes by follicular dendritic cells (FDC) is considered to be a central step in the generation of memory B cells. During this process, which takes place in the microenvironment of the germinal center, B cells and FDC are in close physical contact. In the present study, we have explored the molecular basis of FDC-B cell interaction by using FDC and B cells derived from human tonsils. We found that FDC express high levels of the adhesion receptors intercellular adhesion molecule 1 (ICAM-1 [CD54]) and vascular cell adhesion molecule 1 (VCAM-1), while the B lymphocytes express lymphocyte function-associated antigen 1 (LFA-1 [CD11a/18]), very late antigen 4 (VLA-4 [CD49d], and CD44. Furthermore, we established that both the LFA-1/ICAM-1 and VLA-4/VCAM-1 adhesion pathways are involved in FDC-B lymphocyte binding, and therefore, these pathways might be essential in affinity selection of B cells and in the formation of B memory cells.     

T细胞LFA-1/ICAM-1协同刺激信号的研究进展

LFA—1／ICAM—1信号是T细胞参与免疫反应的重要协同刺激信号。T细胞表面LFA-1对ICAM-1的亲和力及亲合力在TCR/CD3交联MHC／抗原肽后迅速上调，并参与T细胞免疫突触的形成。随后产生的LFA-1／ICAM-1信号通过上调PI-3K、鞘磷脂酶和JNK等激酶活性协同第一信号活化T细胞，从而诱导T细胞分泌1型细胞因子，促进T细胞增殖和增加细胞毒等效应。     

Characterization of the function of intercellular adhesion molecule (ICAM)-3 and comparison with ICAM-1 and ICAM-2 in immune responses

We have characterized the immunobiology of the interaction of intercellular adhesion molecule 3 (ICAM-3; CD50) with its counter- receptor, leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18). Purified ICAM-3 supported LFA-1-dependent adhesion in a temperature- and cation-dependent manner. Activation of cells bearing LFA-1 increased adhesiveness for ICAM-3 in parallel to adhesiveness for ICAM- 1. Although CBR-IC3/1 monoclonal antibody (mAb) blocked adhesion of cells to purified LFA-1, when tested alone, neither CBR-IC3/1 nor five novel ICAM-3 mAbs characterized here blocked adhesion of cells to purified ICAM-3 or homotypic adhesion. Two ICAM-3 mAbs, CBR-IC3/1 and CBR-IC3/2, were required to block LFA-1-dependent adhesion to purified ICAM-3- or LFA-1-dependent, ICAM-1-, ICAM-2-independent homotypic adhesion of lymphoid cell lines. Two ICAM-3 mAbs, CBR-IC3/1 and CBR- IC3/6, induced LFA-1-independent aggregation that was temperature and divalent cation dependent and was completely inhibited by ICAM-3 mAb, CBR-IC3/2, recognizing a distinct epitope. Purified ICAM-3 provided a costimulatory signal for proliferation of resting T lymphocytes. mAb to ICAM-3, together with mAbs to ICAM-1 and ICAM-2, inhibited peripheral blood lymphocyte proliferation in response to phytohemagglutinin, allogeneic stimulator cells, and specific antigen. Inhibition was almost complete and to the same level as with mAb to LFA-1, suggesting the most functionally important, and possibly all, of the ligands for LFA-1 have been defined.     

Importance of integrin LFA-1 deactivation for the generation of immune responses

The dynamic regulation of ligand binding is considered crucial for integrin function. However, the importance of activity regulation for integrin function in vivo is largely unknown. Here, we have applied gene targeting to delete the GFFKR sequence of the lymphocyte function-associated antigen-1 (LFA-1) alpha(L) subunit cytoplasmic domain in mouse germline. Lymphocytes from Lfa-1(d/d) mutant mice showed constitutive activation of LFA-1-mediated cell adhesion and impaired de-adhesion from intercellular adhesion molecule-1 that resulted in defective cell migration. In contrast, signaling through LFA-1 was not affected in Lfa-1(d/d) cells. T cell activation by superantigen-loaded and allogeneic APCs, cytotoxic T cell activity, T-dependent humoral immune responses, and neutrophil recruitment during aseptic peritonitis were impaired in Lfa-1(d/d) mice. Thus, deactivation of LFA-1 and disassembly of LFA-1-mediated cell contacts seem to be vital for the generation of normal immune responses.     

rhG-CSF动员对供者外周血CD4+T细胞极化和迁移的影响

T淋巴细胞极化和迁移的过程需要依赖细胞表面的淋巴细胞功能相关抗原-1（LFA-1）与其配体细胞间粘附分子-1（ICAM-1）的结合。本研究旨在探讨重组人粒细胞集落刺激因子（rhG-CSF）动员对异基因造血干细胞移植（allo-HSCT）供者外周血CD4＋T细胞的极化和迁移的影响。采集10例allo-HSCT供者于rhG-CSF动员后第5天和10例健康志愿者的外周血,使用免疫磁珠分选法纯化CD4＋T细胞,使用激光扫描共聚焦显微镜检测CD4＋T细胞接受基质细胞衍生因子1理（SDF-1d）和ICAM-1信号刺激后细胞的极化和迁移能力。结果显示,rhG-CSF动员后供者CD4＋T细胞的极化比例为（32．424-4．91）％,健康人志愿者为（56．55±5．35）％,差异有统计学意义（P〈0．01）;rhG-CSF动员后供者CD4＋T细胞的迁移速率为（7．06±1．44μm／min）,健康志愿者CD4＋T细胞的迁移速率为（9．05±1．91μm／min）,差异有统计学意义（P〈0．01）。结论：rhG-CSF动员能明显抑制供者CD4＋T细胞的极化和迁移能力。     

重组人粒细胞集落刺激因子动员对CD4+T淋巴细胞迁移和黏附功能的影响

目的探讨重组人粒细胞集落刺激因子(rhG-CSF)动员对CD4+T淋巴细胞表面分子CXCR4和淋巴细胞功能相关抗原1(LFA-1)所介导功能和相关信号机制的影响.方法在rhG-CSF动员前和动员后第5天抽取供者外周血,用三色荧光标记检测动员前后CD4+T淋巴细胞LFA-1和CXCR4的表达率,并应用免疫磁性分选法分离纯化CD4+T淋巴细胞,检测动员前后CD4+T淋巴细胞对基质细胞衍生因子1α(SDF-1α)的迁移能力和对细胞间黏附分子1(ICAM-1)的黏附能力.结果rhG-CSF动员前后CD4+T淋巴细胞的LFA-1(CD11a)和CXCR4表达率差异无统计学意义(P＞0.05),动员前后CD4+T细胞LFA-1表达率均为100%;动员前CD4+T淋巴细胞CXCR4表达率为(84.58±20.31)%,动员后为(81.23±22.46)%.动员前后CD4+T淋巴细胞向SDF-1α的4 h迁移率分别为(28.5±10.3)%和(31.2±8.9)%,差异无统计学意义(P＞0.05);动员前后CD4+T淋巴细胞在CD3单抗作用下对ICAM-1的黏附率分别为(85.59±14.21)%和(61.45±15.07)%,动员前显著高于动员后(P＜0.05).结论rhG-CSF动员不影响CD4+T淋巴细胞LFA-1和CXCR4的表达,但影响CD4+T淋巴细胞通过LFA-1对ICAM-1的黏附能力.     

The Lymphocyte Function–associated Antigen 1 I Domain Is a Transient Binding Module for Intercellular Adhesion Molecule (ICAM)-1 and ICAM-3 in Hydrodynamic Flow

The I domain of lymphocyte function–associated antigen (LFA)-1 contains an intercellular adhesion molecule (ICAM)-1 and ICAM-3 binding site, but the relationship of this site to regulated adhesion is unknown. To study the adhesive properties of the LFA-1 I domain, we stably expressed a GPI-anchored form of this I domain (I-GPI) on the surface of baby hamster kidney cells. I-GPI cells bound soluble ICAM-1 (sICAM-1) with a low avidity and affinity. Flow cell experiments demonstrated a specific rolling interaction of I-GPI cells on bilayers containing purified full length ICAM-1 or ICAM-3. The LFA-1 activating antibody MEM-83, or its Fab fragment, decreased the rolling velocity of I-GPI cells on ICAM-1–containing membranes. In contrast, the interaction of I-GPI cells with ICAM-3 was blocked by MEM-83. Rolling of I-GPI cells was dependent on the presence of Mg²⁺. Mn²⁺ only partially substituted for Mg²⁺, giving rise to a small fraction of rolling cells and increased rolling velocity. This suggests that the I domain acts as a transient, Mg²⁺-dependent binding module that cooperates with another Mn²⁺-stimulated site in LFA-1 to give rise to the stable interaction of intact LFA-1 with ICAM-1.     

The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester

Lymphocytes become adherent and aggregate after stimulation with phorbol esters such as PMA. Time-lapse video showed that aggregating cells were motile and exhibited vigorous pseudopodial movements. Adhesion sites were initiated between pseudopodia of neighboring cells, and then moved to the uropod. PMA-stimulated aggregation by EBV-transformed B cell lines, SKW-3 (a T cell line), differentiated U937 (a monocytic line), and blood lymphocytes was inhibited by mAbs to LFA-1. A number of different mAb to the LFA-1 alpha and beta subunits and F(ab')2 and Fab' fragments inhibited aggregation. Furthermore, lymphoblasts from normal individuals, but not from LFA-1-deficient patients, aggregated in response to PMA. These findings suggest LFA-1 is critically involved in stimulated lymphocyte adhesion. LFA-1 expression was not increased by PMA stimulation, showing that other mechanisms regulate LFA-1-dependent adherence. LFA-1-deficient patient cells were able to coaggregate with LFA-1+ cells, showing that aggregation is not mediated by like-like interactions between LFA-1 molecules on opposite cells. Aggregation was Mg+2-dependent, inhibited by cytochalasin B, and was reversed when LFA-1 mAb was added to preformed aggregates. Previous findings suggesting that LFA-1 is important in a wide variety of leukocyte functions are elucidated by this work, which shows that LFA-1 is a general leukocyte cell adhesion molecule, the activity of which is regulated by cell activation.     

Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut

Integrin adhesion molecules mediate lymphocyte migration and homing to normal and inflamed tissues. While the ligand-binding activity of integrins is known to be modulated by conformational changes, little is known about how the appropriate balance of integrin adhesiveness is maintained in order to optimize the migratory capacity of lymphocytes in vivo. In this study we examined the regulation of the gut homing receptor alpha4beta7 integrin by manipulating at the germline level an integrin regulatory domain known as adjacent to metal ion-dependent adhesion site (ADMIDAS). ADMIDAS normally serves to raise the activation threshold of alpha4beta7, thereby stabilizing it in the default nonadhesive state. Lymphocytes from knockin beta7 (D146A) mice, which harbor a disrupted ADMIDAS, not only expressed an alpha4beta7 integrin that persistently adhered to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but also exhibited perturbed cell migration along MAdCAM-1 substrates resulting from improper de-adhesion of the lymphocyte trailing edge. In vivo, aberrantly activated alpha4beta7 enhanced adhesion to Peyer's patch venules, but suppressed lymphocyte homing to the gut, diminishing the capacity of T cells to induce colitis. Our results underscore the importance of a proper balance in the adhesion and de-adhesion of the alpha4beta7 integrin, both for lymphocyte trafficking to the gut and for colitis progression.     

Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue

To determine the role of vascular cell adhesion molecule 1 (VCAM- 1)/very late activation antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1)/lymphocyte function-associated antigen 1 (LFA-1) interactions in causing antigen-induced eosinophil and T cell recruitment into the tissue, we studied the effect of the in vivo blocking of VCAM-1, ICAM-1, VLA-4, and LFA-1 by pretreatment with monoclonal antibodies (mAb) to these four adhesion molecules on the eosinophil and T cell infiltration of the trachea induced by antigen inhalation in mice. The in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, prevented antigen-induced eosinophil infiltration into the mouse trachea. On the contrary, the in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, increased blood eosinophil counts after antigen challenge, but did not affect blood eosinophil counts without antigen challenge in sensitized mice. Furthermore, the expression of VCAM-1 but not ICAM-1 was strongly induced on the endothelium of the trachea after antigen challenge. In addition, pretreatment with anti-IL-4 mAb decreased the antigen-induced VCAM-1 expression only by 27% and had no significant effect on antigen-induced eosinophil infiltration into the trachea. The in vivo blocking of VCAM- 1 and VLA-4 inhibited antigen-induced CD4+ and CD8+ T cell infiltration into the trachea more potently than that of ICAM-1 and LFA-1. In contrast, regardless of antigen challenge, the in vivo blocking of LFA- 1, but not of ICAM-1, increased blood lymphocyte counts more than that of VCAM-1 and VLA-4. These results indicate that VCAM-1/VLA-4 interaction plays a predominant role in controlling antigen-induced eosinophil and T cell recruitment into the tissue and that the induction of VCAM-1 expression on the endothelium at the site of allergic inflammation regulates this eosinophil and T cell recruitment.     

Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice

Using lymphocyte function-associated antigen (LFA)-1(-/-) mice, we have examined the role of LFA-1 and other integrins in the recirculation of lymphocytes. LFA-1 has a key role in migration to peripheral lymph nodes (pLNs), and influences migration into other LNs. Second, the alpha4 integrins, alpha4beta7 and alpha4beta1, have a hitherto unrecognized ability to compensate for the lack of LFA-1 in migration to pLNs. These findings are confirmed using normal mice and blocking LFA-1 and alpha4 monoclonal antibodies. Unexpectedly, vascular cell adhesion molecule (VCAM)-1, which is essential in inflammatory responses, serves as the ligand for the alpha4 integrins on pLN high endothelial venules. VCAM-1 also participates in trafficking into mesenteric LNs and Peyer's patch nodes where mucosal addressin cell adhesion molecule 1 (MAdCAM-1), the alpha4beta7-specific ligand, dominates. Both alpha4beta1, interacting with ligand VCAM-1, and also LFA-1 participate in substantial lymphocyte recirculation through bone marrow. These observations suggest that organ-specific adhesion receptor usage in mature lymphocyte recirculation is not as rigidly adhered to as previously considered, and that the same basic sets of adhesion receptors are used in both lymphocyte homing and inflammatory responses.     

T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis

Asthma is a disease of airway inflammation and hyperreactivity that is associated with a lymphocytic infiltrate in the bronchial submucosa. The interactions between infiltrating T lymphocytes with cellular and extracellular matrix components of the airway and the consequences of these interactions have not been defined. We demonstrate the constitutive expression of CD44 on human airway smooth muscle (ASM) cells in culture as well as in human bronchial tissue transplanted into severe combined immunodeficient mice. In contrast, basal levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression are minimal but are induced on ASM by inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha). Activated, but not resting T cells, adhere to cultured ASM; stimulation of the ASM with TNF-alpha enhanced this adhesion. Adhesion was partially blocked by monoclonal antibodies (mAb) specific for lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) on T cells and ICAM-1 and VCAM-1 on ASM cells. The observed integrin-independent adhesion was mediated by CD44/hyaluronate interactions as it was inhibited by anti-CD44 mAb 5F12 and by hyaluronidase. Furthermore, the adhesion of activated T lymphocytes induced DNA synthesis in growth-arrested ASM cells. Thus, the interaction between T cells and ASM may provide insight into the mechanisms that induce bronchial inflammation and possibly ASM cell hyperplasia seen in asthma.     

LFA-1和VLA-4参与人高增殖潜能内皮祖细胞与血管内皮的黏附和跨内皮迁移

为了了解淋巴细胞功能相关抗原1（lymphocyte function—associated antigen1，LFA-1）和极迟反应抗原4（very lateantigen 4，VLA-4）在高增殖潜能内皮祖细胞（high proliferative potential endothelial progenitor cells，HPP—EPCs）归巢过程中与血管内皮的黏附和跨内皮迁移中的作用，利用流式细胞术检测HPP—EPC中整合蛋白B1和B2的表达以及小鼠骨髓内皮细胞相应的受体的表达。利用体外黏附和迁移实验研究经过功能级别的中和抗体阻断VLA-4和LFA-1后HPP—EPC黏附和迁移细胞数目的变化。结果表明，HPP—EPC表达整合蛋白B1和B2，活化后小鼠骨髓内皮细胞表达细胞间黏附分子1（intercellular adhesion molecule1，ICAM-1）和血管细胞黏附分子1（vascular cell adhesion molecule1，VCAM-1）；加CDlla抗体组黏附细胞或CD49d抗体组黏附和迁移细胞均较同型对照抗体组少，而且加CDlla和CD49d两种抗体联用组黏附和迁移细胞明显减少，其细胞数较任何单一抗体组少。结论：LFA-1和VLA-4在HPP—EPC与血管内皮的黏附和跨内皮迁移中发挥了重要的作用。     

Orchestration of lymphocyte chemotaxis by mitochondrial dynamics

Lymphocyte traffic is required to maintain homeostasis and perform appropriate immunological reactions. To migrate into inflamed tissues, lymphocytes must acquire spatial and functional asymmetries. Mitochondria are highly dynamic organelles that distribute in the cytoplasm to meet specific cellular needs, but whether this is essential to lymphocyte functions is unknown. We show that mitochondria specifically concentrate at the uropod during lymphocyte migration by a process involving rearrangements of their shape. Mitochondrial fission facilitates relocation of the organelles and promotes lymphocyte chemotaxis, whereas mitochondrial fusion inhibits both processes. Our data substantiate a new role for mitochondrial dynamics and suggest that mitochondria redistribution is required to regulate the motor of migrating cells.     

Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism

Inducible cell adhesion molecule 110 (INCAM-110) is a 110-kD glycoprotein expressed on cytokine-activated human vascular endothelial cells. mAb blocking studies indicate that INCAM-110 and intercellular adhesion molecule 1 (ICAM-1) independently support the adhesion of lymphocytes to activated human umbilical vein endothelial cell monolayers. Anti-CD11a/CD18 antibodies with anti-INCAM-110 mAb E1/6 produce greater inhibition of lymphocyte adhesion than either reagent alone, suggesting that INCAM-110 and LFA-1 are not an obligate receptor-ligand pair. Blood monocytes, but not polymorphonuclear leukocytes, also appear to bind endothelial INCAM-110. Endothelial expression of INCAM-110 is upregulated at sites of inflammation, suggesting a role in the recruitment of mononuclear leukocytes.     

体外rhG-CSF刺激对健康人外周血CD4^＋T细胞黏附和极化的影响

T淋巴细胞黏附和极化过程的完成需要依赖细胞表面的淋巴细胞功能相关抗原-1（LFA-1）与其配体细胞间黏附分子-1（ICAM-1）的结合。本研究旨在探讨体外重组人粒细胞集落刺激因子（rhG-CSF）对健康人外周血CD4^＋T细胞的黏附和极化的影响。采集12例健康志愿者的外周血,使用免疫磁珠分选法纯化CD4^＋T细胞,加入rhG-CSF体外培养24 h,检测CD4^＋T细胞接受基质细胞衍生因子1α（SDF-1α）和ICAM-1信号刺激后细胞的黏附和极化的能力。结果显示,实验组（体外rh G-CSF作用后的健康志愿者）CD4^＋T细胞的黏附比例为（61.9±5.9）%,对照组（健康志愿者）为（68.3±7.3）%,差异有统计学意义（P〈0.05）;实验组（体外rh G-CSF作用后的健康志愿者）CD4^＋T细胞的极化比例为（24.3±4.3）%,对照组（健康志愿者）为（47.1±5.1）%,差异有统计学意义（P〈0.05）。结论：体外rh G-CSF能抑制健康者外周血CD4^＋T细胞黏附和极化的能力。