趋化因子及受体与中国HCV/HIV合并感染相关性的研究

目的：探讨趋化因子自细胞介素8（IL-8）、干扰素诱导蛋白10（IFN-inducible 10-kdaprotein，IP-10）及趋化因子受体CCR5、CXCR3，在丙肝病毒（HCV）单纯感染，艾滋病病毒（HIV）单纯感染和HCV／HIV合并感染过程中的表达及意义。方法：采用流式细胞术，检测HCV感染组（n=21）、HIV感染组（n=14）、HCV／HIV感染组（n=28）及正常对照组（n=30）人外周血CD4^＋T淋巴细胞和CD8^＋T淋巴细胞表面CCR5、CXCR3的表达。ELISA方法检测血清趋化因子IL-8、IP-10含量。结果：HCV感染组、HIV感染组和HCV／HIV合并感染组，血清IP-10水平都明显升高，而在合并感染组水平最高；血清IL-8水平在3组亦明显升高。HIV感染组及HCV／HIV合并感染组CD4^＋T细胞表面CXCR3表达显著降低（P〈0．001），CD8^＋T细胞表面CXCR3表达显著升高（P〈0．001）；HCV感染组CD4^＋及CD8^＋T细胞表面CXCR3表达轻度升高，但差异不显著。HCV感染组及HCV／HIV合并感染组CD4^＋及CD8^＋T细胞表面CCR5表达显著降低（P〈0.001）；HIV感染组CD4^＋及CD8^＋T细胞表面CCR5表达显著升高（P〈0.001）。结论：中国HCV／HIV合并感染患者中，血清IL-8和IP-10水平都明显升高；受体CXCR3在CD4^＋T细胞表面表达降低，而在CD8^＋T细胞表面表达升高；受体CCR5在CD4^＋及CD8^＋T细胞表面表达降低，提示趋化因子及受体与HCV／HIV合并感染密切相关。     

慢性乙型肝炎患者外周血淋巴细胞上CXCR3表达的初步观察

目的：探讨趋化性细胞因子受体CXCR3在慢性乙型肝炎症发生机制中的作用。方法：采用流式细胞术，检测炎症活动程度不同患者外周血淋巴细胞表面CXCR3的表达，及其在CD4^ 和CD8^ T细胞上的分布。结果：慢性乙肝患者外周血CXCR3^ 淋巴细胞和单核细胞明显增多，以CXCR3^ CD8^ T细胞的增加更明显。结论：趋化因子受体CXCR3与其配体的相互作用，可能在募集淋巴细胞及炎症形成过程中有重要作用。     

HIV-1感染者淋巴细胞活化与第二受体表达的研究

目的：了解HIV－1感染者体内淋巴细胞的活化情况及表达第二受体CCR5、CXCR4的淋巴细胞活化状态，分析这些指标与疾病严重程度的关系，探讨HIV感染的免疫基础。方法：用三色标记法流式细胞术检测24例HIV－1感染者及13例健康对照的抗凝血标本，分析活化标志物HLA－DR及第二受体CCR5、CXCR4的表达等指标。结果：HIV－1感染者CD8^ T淋巴细胞的HLA－DR表达高于健康对照（P＜0．001）；HIV－1感染者表达CCR5、CXCR4的CD8^ T淋巴细胞活化明显高于健康对照（P＜0．001）；表达CCR5CD4^ 、CD8^ T淋巴细胞与表达CXCR4相比HL－DR表达均明显增高（P＜0．001）；CD4^ 、CD8^ T淋巴细胞的活化状态与CD4百分率的变化明显关系。结论：HIV－1感染者CD8^ T淋巴细胞及表达不同第二受体的CD8^ T淋巴细胞活化程度明显增高，活化程度与疾病进程相关。     

慢乙肝患者外周血中Th17细胞趋化因子受体的表达水平

目的 检测慢性乙型病毒性肝炎（chronic hepatitis B,CHB）患者外周血中Th17细胞表面趋化因子受体CCR4、CCR6、CXCR3的表达,分析CCR4、CCR6、CXCR3与丙氨酸转氨酶（ALT）、总胆红素（TBil）及HBV DNA载量的相关性.方法 流式细胞仪检测30例CHB患者（CHB组）及15名健康人（对照组）外周血中Th17细胞CCR4、CCR6、CXCR3的表达,与ALT、TBil、HBV DNA载量进行相关性分析.结果 CHB组CD4＋ Th17细胞CCR4、CCR6、CXCR3的表达水平高于对照组,其差异有统计学意义（P＜0.05）.CHB组CD8＋ Th17细胞CCR4、CCR6的表达水平高于对照组,其差异有统计学意义（P＜0.05）.CCR4、CCR6表达水平与ALT、HBV DNA载量呈正相关（P＜0.05）,与TBil水平无相关性（P＞0.05）.结论 CHB患者外周血中Th17细胞表面CCR4、CCR6表达增高,与炎症程度相关,可能涉及Th17细胞引起的肝损伤.     

HIV/AIDS患者CCR5、CXCR4的表达与疾病进展的关系

目的　了解HIV AIDS患者淋巴细胞表面第二受体CCR5、CXCR4的表达 ,分析其与疾病进展的关系 ,探讨HIV感染的免疫基础。方法　收集 33例HIV AIDS患者及 13例健康对照的抗凝全血 ,用流式细胞仪检测第二受体CCR5、CXCR4的表达 ,并分析第二受体表达与病毒载量、CD4 + T淋巴细胞绝对值及T淋巴细胞活化 (HLA DR+ CD38+ )的相关性。结果　艾滋病组CD4 + 、CD8+ T淋巴细胞表面CCR5表达高于无症状HIV 1感染组及健康对照 (P <0 .0 0 1) ;艾滋病组CD8+ T淋巴细胞表面CXCR4表达低于健康对照 (P <0 .0 1)。HIV AIDS患者CD4 + 、CD8+ T淋巴细胞表面CCR5的表达与病毒载量明显正相关 (P <0 .0 1) ;与CD4 + T淋巴细胞绝对值明显负相关 (P <0 .0 1) ,与T淋巴细胞活化(HLA DR+ CD38+ )水平明显正相关 (P <0 .0 0 1)。结论　HIV 1感染者第二受体CCR5的表达与机体对HIV的免疫反应及疾病进展密切相关。     

ConA刺激对CD4+CD25+调节性T细胞趋化特性及其表面趋化因子受体CCR4/CCR6表达的影响

目的：体外动态观察ConA激活的调节性T细胞表面趋化因子受体的表达变化及其趋化特性，为利用调节性T细胞诱导免疫耐受提供线索。方法：①流式细胞仪分选出CD4hiCD12710CD25 hiint细胞。②纯化的调节性T细胞与CD4^＋CD25一T细胞分别用ConA（10Fg／m1）刺激0、24和48小时后，用趋化因子CCL1、CCI5、CCL20、CCI_22做趋化实验，观察各趋化因子作用下调节性T细胞与CD4^＋CD25-T细胞的趋化特性。同时，流式细胞仪检测CCR4与CCR6的表达。结果：①分离得到的调节性T细胞纯度为97．4％，活细胞率为95％，得率：4．1％。②CCL1、CCL20、CCL22均可趋化调节性T细胞，且在ConA激活后趋化效率随时间而改变。CCL1与CCL22对调节性T细胞的趋化指数显著高于CD4^＋CD25^-T细胞；CCL20对调节性T细胞和CD4^＋CD25-T细胞趋化指数都很高；CCL5对调节性T细胞趋化性则显著弱于CD4^＋CD25^-T细胞。③ConA刺激后，调节性T细胞趋化因子受体CCR4、CCR6的表达均明显高于对照组细胞（CD4^＋CD25^-细胞）。随着ConA刺激时间延长，两组细胞CCR4的表达均持续增强；两组细胞CCR6的表达均在刺激24小时后表达明显增强，48小时后CCR6的表达略有减弱，呈下降趋势。结论：①磁珠阴性分选结合流式细胞仪技术可分选出较高纯度及活率的调节性T细胞。②调节性T细胞与CD4^＋CD25^-T细胞相比，二者具有不同的趋化特性。CCL1对调节性T细胞的趋化作用较特异，CCL-22趋化作用较强，CCL5趋化作用较弱。而CCL20对CD4^＋CD25-T细胞和调节性T细胞趋化作用都强。③ConA刺激后48小时内趋化因子CCLl、CCL20、CCL-22对调节性T细胞的趋化作用随刺激时间而增强。④ConA刺激可以增强受体CCR4、CCR6表达。⑤提示趋化因子受体的表达与细胞活化状态有关，且不同受体表达变化趋势不同。     

风湿性关节炎患者T细胞表达CCR5和CXCR3的三色流式细胞分析

目的 在单细胞水平上，研究类风湿性关节炎（RA）患者滑液及外周血中T淋巴细胞上CCR5及CXCR3的表达，并结合临床资料分析其在RA发病中的可能作用机制及临床应用。方法 分离15例RA患者的滑液单个核细胞（SFMC）、外周血单个核细胞（PBMC），及15正常人PBMC（对照），以三色荧光素标记物进行流式细胞术分析T细胞上CCR5及CXCR3的表达。结果 与PBMC相比较，RA患者SFMC中T细胞上CCR5及CXCR3的表达显著增高（特别是CCR5）；而CXCR3的表达个体差异较大；与正常人相比较，RA患者初发或活动期未治时，PBMC中CCR5及CXCR3的表达明显增多。CCR5及CXCR3的表达率与患者的ESR及CRP相关。结论 CCR5^ T细胞积聚在RA患者的病变关节内，且与RA的病情密切相关。     

多器官功能障碍综合征小鼠肺间质树突状细胞的病理学观察

目的探讨肺间质树突状细胞在多器官功能障碍综合征（MODS）免疫紊乱及脏器损伤机制中的变化与作用。方法C57BL／6小鼠腹腔注射酵母多糖复制MODS模型,分为正常、3—6h（致伤早期）、12～48h[失控性全身炎性反应（SIRS）期]、5～7d（恢复期）和10～12d（MODS期）组。光镜与电镜观察各组小鼠肺及间质树突状细胞的病变;运用免疫组织化学方法检测间质树突状细胞表面标记物CD11c和CD205,共刺激分子CD80和CD86在肺中的表达水平;逆转录-聚合酶链反应法检测趋化因子SLC及其受体CCR7在肺中的表达情况;流式细胞术检测MODS各期小鼠外周血CD4^＋与CD8^＋的T淋巴细胞数量与比值。结果致伤早期,肺间质树突状细胞显著增生,共刺激分子CD80和CD86低水平表达,趋化因子SLC及其受体CCR7在肺组织中表达水平开始上升,外周血T淋巴细胞CD4^＋／CD8^＋比值下降;SIRS期,间质树突状细胞继续增生,CD80和CD86标记阳性细胞数显著上升（与正常组比较均P〈0．01）,SLC与CCR7在肺组织中表达明显高于正常组（均P〈0．01）,外周血T淋巴细胞CD4^＋／CD8^＋比值明显下降（与正常组比较P〈0．01）;MODS期,肺间质树突状细胞高度增生,但CD80和CD86表达显著减少（与SIRS期比较P〈0．01）,肺组织中SLC表达水平继续上升,而CCR7表达水平明显下降（与SIRS期比较P〈0．01）,外周血T淋巴细胞CD4^＋／CD8^＋比值显著下降。结论肺间质树突状细胞在MODS中的变化可能参与并影响了MODS病程中的免疫失衡与免疫抑制过程。CCR7的表达水平可以作为估价间质树突状细胞迁移活性和机体免疫应答水平的一个指标。     

人早孕蜕膜基质细胞及免疫活性细胞趋化因子受体CXCR6的表达

目的分析人早孕期蜕膜基质细胞趋化因子配基受体对CXCL16/CXCR6的表达及免疫活性细胞趋化因子受体CXCR6的表达,以探讨CXCL16/CXCR6在蜕膜免疫活性细胞募集中的可能规律.方法收集早孕期蜕膜组织,分离蜕膜基质细胞和免疫细胞,分别采用半定量RT-PCR、免疫细胞化学、流式细胞术分析蜕膜基质细胞CXCL16和CXCR6的表达;流式细胞术分析蜕膜CD56^＋CD16^-NK细胞、CD56^＋CD16^＋NK细胞、NKT细胞、T细胞、γδT细胞、单核细胞CXCR6的表达.结果人早孕蜕膜基质细胞高水平转录趋化因子受体CXCR6,低水平转录其配体CXCL16,但CXCL16和CXCR6在蛋白水平的表达偏低.早孕蜕膜γδT细胞CXCR6阳性率为87.29%;CD14^＋单核细胞CXCR6阳性率为47.71%;NKT细胞CXCR6阳性率为44.14%;T细胞CXCR6表达率为32.91%;而蜕膜两种NK细胞（CD56^＋CD16^-、CD56^＋CD16^＋）几乎不表达CXCR6.结论人γδT细胞、单核细胞、NKT细胞、T细胞可能通过表达趋化因子受体CXCR6被募集到蜕膜局部并驻留,从而参与早孕期母胎界面的免疫调节.     

强直性脊柱炎患者外周血免疫细胞比例及CXCR6表达水平的研究

为研究强直性脊柱炎(ankylosing spondylitis, AS)患者外周血中免疫细胞比例以及趋化因子受体CXCR6的表达水平对AS的影响,检测AS患者和健康对照者血常规、CRP和ESR,分析AS患者的炎症情况;流式细胞术分析淋巴细胞亚群比例以及CXCR6在外周血CD3~+T淋巴细胞、CD4~+T淋巴细胞和γδT细胞上的表达水平,并分析髓源抑制细胞(myeloid-derived suppressor cell, MDSC)和Treg水平。研究发现AS患者中性粒细胞绝对值、CRP、ESR、CD3~+T淋巴细胞、CD4~+T淋巴细胞、NK细胞、γδT细胞和MDSC的比例明显高于对照组(P0.05),而Treg比例没有明显差异。同时,CXCR6在CD3~+T淋巴细胞、CD4~+T淋巴细胞和γδT细胞的表达水平高于对照组(P0.05)。研究表明外周血中CD3~+T淋巴细胞、CD4~+T淋巴细胞、γδT细胞和MDSC等免疫细胞的比例升高且CXCR6参与AS外周免疫细胞的招募,这些因素在AS炎症反应中发挥重要作用。     

Selective recruitment of CXCR3+ and CCR5+ CCR4+ T cells into synovial tissue in patients with rheumatoid arthritis

The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.     

Graves' disease is associated with an altered CXCR3 and CCR5 expression in thyroid-derived compared to peripheral blood lymphocytes

The mechanisms by which T cells accumulate in the thyroid and support the autoimmune process in patients with Graves' disease (GD) are poorly understood. Chemokines and their receptors may be involved in this process. We have analysed the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2 (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid-derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on PBL of GD patients (n = 16) did not differ from that of normal controls (n = 10). In GD, CXCR3+ (67.3 +/- 4.0% versus 45.7 +/- 2.1%) and CCR5+ T cells (42.5 +/- 3.4% versus 18.8 +/- 2.1%) showed a significant enrichment in the TL compared to PBL. The positive cells were contributed mainly by the CD4+CD45R0+ subset. TL are mostly primed CD45R0+ T cells, but surprisingly, they had significantly higher levels of CXCR4+ cells among TL (96.2 +/- 1.0%) compared to PBL (66.8 +/- 4.2%). However, CXCR4 has been induced during in vitro isolation of TL. There was no correlation between chemokine receptors and the level of TSH-receptor and thyroid peroxidase autoantibodies. CCR3+ and CCR2+ cells remained unchanged in TL compared to PBL. We could confirm the results using RT PCR and immunohistology. In summary, TL showed a different chemokine receptor pattern compared to PBL from the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of T cells to the thyroid in GD.     

CXCR3 and CCR5 are both required for T cell-mediated protection against C. trachomatis infection in the murine genital mucosa

Chemokine receptors direct T lymphocytes to the site of an infection by following coordinated chemokine gradients, which allow their recruitment to specific tissues. Although identification of receptors needed for homing to some mucosal sites, such as skin and gut, have been elucidated, the receptors that direct lymphocytes to the genital mucosa remain relatively uncharacterized. In this study we identify that the chemokine receptors CXCR3 (chemokine (C-X-C motif) receptor 3) and CCR5 (chemokine (C-C motif) receptor 5) are pivotal for T-lymphocyte access to the genital tract during Chlamydia trachomatis infection. Chlamydia-specific CD4⁺ transgenic T cells that lack CXCR3 or CCR5 do not accumulate in the genital mucosa following infection. Loss of either CXCR3 or CCR5 impairs the protective capacity of Chlamydia-specific T cells, whereas T cells lacking both receptors are completely nonprotective. These results show that CXCR3 and CCR5 are the predominant chemokine receptors that act cooperatively to promote homing to the genital mucosa during Chlamydia infection.     

Adenoids provide a microenvironment for the generation of CD4(+), CD45RO(+), L-selectin(-), CXCR4(+), CCR5(+) T lymphocytes, a lymphocyte phenotype found in the middle ear effusion

Adenoidectomy in children with otitis media with effusion reduces inflammation in the middle ear by an unknown mechanism. Potentially, the adenoids of these children may serve as a site for the differentiation of lymphocytes, which after entering blood circulation eventually extravasate in the middle ear mucosa and thereby contribute to excessive inflammation. During lymphocyte extravasation various adhesion molecules and chemokines play a crucial role. To evaluate possible connections between the adenoids and middle ear inflammation, the expression of the chemokine receptors CXCR4 and CCR5 and the lymphocyte homing receptor L-selectin were analyzed in adenoidal and middle ear lymphocytes. It was found that most CD4(+) T lymphocytes in the middle ear effusion express the memory phenotype marker CD45RO and the chemokine receptors CXCR4 and CCR5, but are negative for the lymphocyte homing receptor L-selectin. This cell phenotype was rare in peripheral blood but was found much more frequently in the adenoids. The results suggest that the adenoids provide a microenvironment for the generation for CD4(+), CD45RO(+), L-selectin(-), CXCR4(+) and CCR5(+) T lymphocytes. Further, these cells may include cells that have the capacity to home to the middle ear mucosa. As the adenoidal CD4(+) memory phenotype CD45RO(+) T cells expressed the activation antigen CD69 and included cells expressing the HIV co-receptors CXCR4 and CCR5 at a high level, they may be permissive for HIV infection.     

Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes.

Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4(+) lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4(+) populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue-infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4(+) lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra-lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69(+)). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in alpha(4)beta(7) expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation.     

早、中、晚孕期胎盘因子对人外周血淋巴细胞CD4、CCR5和CXCR4表达的影响

目的 通过研究早、中、晚孕期胎盘因子(PF)对人外周血淋巴细胞(PBLs)中CD4、CCR5和CXCR4表达的作用,探讨PF在人免疫缺陷病毒-1(HIV-1)垂直传播中的作用及其机理.方法 制备早、中、晚孕期PF.分离人外周血单个核细胞,并分别与相对浓度为25%的早、中、晚孕期PF作用,培养24 h后收集细胞,荧光抗体标记,流式细胞术检测外周血淋巴细胞(PBLs)中CD4、CCR5和CXCR4表达,以及CD4 T细胞中CCR5 细胞、CXCR4 细胞、CCR5 CXCR4 细胞所占的百分率.结果 各孕期PF均可显著降低PBLs中CCR5的表达,其中早孕期PF的作用明显强于中、晚孕期PF的作用;各孕期PF组CD4 T细胞中CCR5 细胞的百分率均显著低于对照组,早孕期PF组CD4 T细胞中CCR5 细胞的百分率明显低于中、晚孕期PF组;各孕期PF组CD4 T细胞中CCR5 CXCR4 细胞的百分率均显著低于对照组,早孕期PF组CD4 T细胞中CCR5 CXCR4 细胞的百分率显著低于晚孕期PF组.结论 各孕期PF均可显著降低PBLs中CCR5的表达,以及CD4 T细胞中CCR5 细胞和CCR5 CXCR4 细胞的百分率,早孕期PF作用最强,中、晚孕期PF效应相当,PF可能通过抑制R5病毒的人胞而具有抗R5病毒的作用,并可能在阻断HIV-1宫内感染中具有重要作用.     

CCR4 is an up-regulated chemokine receptor of peripheral blood memory CD4+ T cells in Crohn's disease

Several chemokine receptors are expressed selectively on the surface of T cells depending on their polarization. The aim of this study was to characterize chemokine receptor expression in peripheral blood memory T cells in Crohn's disease (CD) and ulcerative colitis (UC), and to correlate the expression with disease activity. Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with CD, 30 patients with UC, 24 normal controls and 10 disease controls. PBMCs were stained by anti-CCR3, CCR4, CCR5, CXCR3, CD4, CD8, CD45RO and beta 7 integrin, and the expression of the chemokine receptors were determined by flow cytometry. CCR4 expression on memory T cells was significantly lower in UC than in CD or normal controls, and that of memory CD4+ T and beta 7(high) memory CD4+ T cells was significantly higher in CD than in UC or normal controls. CCR4 expression on memory CD4+ T cells exhibited significant positive correlation with disease activity in CD, and this decreased significantly after treatment. Such a decrease was not found in the disease controls. CCR5 and CXCR3 expression on memory CD8+ T cells was significantly lower in CD than in normal controls. CXCR3 expression on beta 7(high) memory CD4+ T and CXCR3 expression on memory CD8+ T cells were lower in UC than in normal controls. These findings suggest that in peripheral blood memory T cells, chemokine receptor expression is different between CD and UC. Enhancement of CCR4 and suppression of CCR5 and CXCR3 seem to be the characteristic chemokine receptor profile in peripheral blood memory T cells of CD.     

Human intestinal lamina propria and intraepithelial lymphocytes express receptors specific for chemokines induced by inflammation

To determine which chemokine receptors might be involved in T lymphocyte localization to the intestinal mucosa, we examined receptor expression on human intestinal lamina propria lymphocytes (LPL), intraepithelial lymphocytes (IEL) and CD45RO+beta7hi gut homing peripheral blood lymphocytes (PBL). Virtually all LPL and IEL expressed CXCR3 and CCR5, receptors that have been associated with Th1(Tc1)/Th0 lymphocytes, while CCR3 and CCR4, receptors associated with Th2 (Tc2)lymphocytes, CCR7, CXCR1 and CXCR2 were not expressed. CXCR3 and CCR5 receptors were functional, as LPL and IEL migrated to their respective ligands I-TAC and RANTES. In addition, most alphaEbeta7- LPL and IEL expressed high levels of CCR2. While the majority of CD45RO(-)beta7hi PBL also expressed CXCR3 and CCR5, a proportion of these cells were CXCR3- and/or CCR5- and some expressed CCR4 and/or CCR7, indicating that lymphocytes recruited to the intestinal mucosa represent a subset of these cells. In summary, our results show that LPL and IEL within the normal intestine express a specific and similar array of chemokine receptors whose ligands are constitutively expressed in the intestinal mucosa and whose expression is up-regulated during intestinal inflammation. These results support the view that CXCR3, CCR5 and CCR2 may play an important role in lymphocyte localization within the intestinal mucosa.