Murphy W J, Tian Z G, Asai O, Funakoshi S, Rotter P, Henry M, Strieter R M, Kunkel S L, Longo D L, Taub D D
Biological Carcinogenesis and Development Program, Science Applications International Corporation-Frederick, MD 21702 USA.
J Immunol. 1996 Mar 15;156(6):2104-11.
Previous studies from this laboratory have demonstrated that the chemokines RANTES (recombinant human regulated upon activation, normally T cell expressed and presumably secreted), macrophage chemotactic peptide-1, recombinant human macrophage inflammatory protein-1 alpha (rhMIP-1 alpha) IL-8, and IP-10 are capable of inducing human T cell infiltration into the injection site of severe combined immunodeficiency (SCID) mice reconstituted with human PBL. However, the ability of these chemokines to facilitate T cell homing into various lymphoid tissues has not been examined. Initial studies focused on the ability of rhMIP-1 beta to induce human T cell infiltration into injection sites in human PBL-SCID mice. SCID mice received s.c. injections of rhMIP-1 beta or PBS (1 microgram/injection) in the hindflank for 4 h or sequential injections for 3 days. Biopsies of the MIP-1 beta injection site revealed the presence of significant mononuclear cell accumulation 72 h after injection. Immunohistologic evaluation determined that significant numbers of human CD3+ T cells were recruited in response to MIP-1 beta injections, and this infiltration could be specifically blocked by co-administration of anti-MIP-1 beta antiserum. We subsequently examined these chemokine-injected mice for the effect of trafficking of human T cells to peripheral lymphoid organs. Flow cytometric analysis of the thymus in human PBL-SCID mice revealed that treatment with rhMIP-1 beta or rhRANTES, but not platelet factor-4, resulted in improved thymic homing of the human T cells after 72 h. This trafficking effect was shown to be direct, as pretreatment of the human T cells with the chemokines in vitro also improved peripheral lymphoid trafficking of the human cells. In addition, co-injection of rhMIP-1 beta with anti-1 beta antiserum abrogated the increase in T cell homing to the thymus. These data demonstrate that MIP-1 beta and RANTES directly augment human T cell trafficking to peripheral murine lymphoid tissues. Chemokines may, therefore, under either isogeneic or xenogeneic conditions, play a role in normal lymphocyte recirculation and homing, and may be of potential clinical use in promoting immune cell trafficking and function.
本实验室先前的研究表明，趋化因子RANTES（重组人活化调节正常T细胞表达和可能分泌因子）、巨噬细胞趋化肽-1、重组人巨噬细胞炎性蛋白-1α（rhMIP-1α）、IL-8和IP-10能够诱导人T细胞浸润到用人外周血淋巴细胞（PBL）重建的严重联合免疫缺陷（SCID）小鼠的注射部位。然而，这些趋化因子促进T细胞归巢到各种淋巴组织的能力尚未得到研究。最初的研究集中在rhMIP-1β诱导人T细胞浸润到PBL-SCID小鼠注射部位的能力上。SCID小鼠在后侧腹皮下注射rhMIP-1β或PBS（1微克/注射），持续4小时或连续注射3天。对MIP-1β注射部位进行活检发现，注射72小时后有大量单核细胞聚集。免疫组织学评估确定，注射MIP-1β后招募了大量人CD3+T细胞，并且这种浸润可通过共同给予抗MIP-1β抗血清而被特异性阻断。随后，我们检查了这些注射趋化因子的小鼠中人类T细胞向外周淋巴器官迁移的影响。对PBL-SCID小鼠胸腺进行流式细胞术分析发现，用rhMIP-1β或rhRANTES处理，但不用血小板因子-4处理，72小时后可改善人T细胞向胸腺的归巢。这种迁移效应被证明是直接的，因为在体外用人T细胞预先处理趋化因子也改善了人细胞向外周淋巴组织的迁移。此外，将rhMIP-1β与抗MIP-1β抗血清共同注射可消除T细胞向胸腺归巢的增加。这些数据表明，MIP-1β和RANTES直接增强人T细胞向外周鼠类淋巴组织的迁移。因此，趋化因子在同基因或异种条件下，可能在正常淋巴细胞再循环和归巢中起作用，并且在促进免疫细胞迁移和功能方面可能具有潜在的临床应用价值。
