树突状细胞向淋巴结归巢的研究进展

树突状细胞（DC）作为专职抗原递呈细胞在诱导机体产生抗肿瘤免疫应答过程中发挥重要作用。以此为基础制备的DC肿瘤疫苗在抗肿瘤免疫治疗中显示出一定的疗效。体外回输DC迁移归巢至局部引流淋巴结是激发特异性免疫应答的关键步骤,归巢DC的数目直接影响免疫应答的强度。了解DC体内归巢至淋巴结的机制,促进DC向淋巴结迁移对于提高DC疫苗的抗肿瘤效果具有重要意义。趋化因子和相应受体、黏附分子、基质金属蛋白酶和脂类介质等多种因素共同调控DC向淋巴结归巢,其中CCR7及其配体CCL19和CCL21是一组最受关注的因子。     

The appearance of non-specific antibody-forming cells in the efferent lymph draining antigen-stimulated single lymph nodes.

Immunization of single lymph nodes with various antigens led to the appearance of cells in the efferent lymph that secreted antibody specific for the antigen which induced their formation and for a number of unrelated, non-crossreacting antigens. Immunization of single lymph nodes with mitogens led to the appearance of cells secreting antibodies specific for an even greater number of antigens, including one (TNP) that in all probability is not present in the animals' natural environment. When the node was primed with one antigen, a subsequent challenge with an unrelated antigen 12 weeks later led to the appearance of greater numbers of cells containing and secreting antibody against the previously experienced antigen, than was the case in unprimed lymph nodes. These findings indicate that the immune response to antigen provokes the maturation of lymphocytes of specificities unrelated to that of the injected immunogen. Such a mechanism may be important in maintaining immunological memory. Mitogens may directly activate lymphocytes into maturation and expression as antibody-secreting cells, whereas antigens appear to act indirectly.     

Dendritic cell subsets in lymph nodes are characterized by the specific draining area and influence the phenotype and fate of primed T cells

Dendritic cells (DC) are important in differential T-cell priming. Little is known about the local priming by DC in the microenvironment of different lymph nodes and about the fate of the imprinted T cells. Therefore, freshly isolated rat DC from mesenteric lymph nodes (mLN) and axillary lymph nodes (axLN) were phenotyped and cultured with blood T cells in the presence of the superantigen Mycoplasma arthritidis mitogen (MAM). The phenotype, proliferation and apoptosis of the primed T cells were analysed. Our data show that a common DC population exists in both mLN and axLN. In addition, region-specific DC with an organotypical marker expression imprinted by the drained area were found. Coculture of T cells with DC from mLN or axLN resulted in a distinct shift in the CD4 and CD8 expression of T cells and their phenotype. Furthermore, when these differentially primed mLN and axLN T cells were injected into recipients, mLN-primed T cells survived longer in other lymphoid organs. The results show that the region-specific DC have a unique phenotype and an impact on the ratio of CD4 : CD8 T cells during an immune response in vivo.     

Microvascular changes in lymph nodes draining skin allografts.

Histological, histochemical, ultrastructural, and radiolabeling characteristics of the microvasculature in regional nodes draining skin allograft sites are described. From 12 to 48 hours after grafting, these nodes show increased vascular permeability and altered lymphocyte traffic pattern. The rapid rise in lymphocyte migration indices and the apparent plugging of intermediate sinuses by lymphocytes suggest that both increased entry and decreased egress of recirculating cells contribute in "lymphocyte trapping." This is followed by redistribution of cortical capillary arcades as existing germinal centers dissolve and proliferating lymphocytes infiltrate the cortex. Normal microvascular patterns reappeared at 7 to 14 days as primary and secondary nodules form in the enlarged nodes. Increased length and arborization of high endothelial venules resulted from focal proliferation of endothelial cells in transition zones from high to low endothelium. In stimulated nodes, high endothelial cells exhibit increased cytoplasmic basophilia and acid hydrolase activities which correlate with the appearance of numerous polyribosomes, RER cisternae, and lysosomes in their cytoplasm. These "activated" endothelial cells phagocytose microthrombi within venular lumens.     

Dendritic cell populations in Leishmania major-infected skin and draining lymph nodes

Using a metacyclic promastigote ear infection model of cutaneous leishmaniasis, we examined the phenotype, parasite load, and cytokine production of dendritic cells in the skin and draining lymph nodes of resistant C57BL/6J and susceptible BALB/c mice. Five dendritic cell populations were isolated from the skin and lymph nodes, and the main difference between the groups of mice was an increased number of plasmacytoid dendritic cells in the lymph nodes of the susceptible mice. Although similar cell types were present in the skin emigrants of both strains, there was a 10-fold larger number of cells in BALB/c mouse skin early in infection than in C57BL/6J mouse skin. None of the dendritic cells in the lymph nodes harbored parasites until 3 weeks after infection, with the Langerhans cells having the largest load and the plasmacytoid dendritic cells having the smallest load but the longest lasting infection. Although parasites could be detected in the lymph nodes a few hours after infection, none of the skin emigrants harbored parasites, indicating that they are not the vehicle that ferries the parasites from the skin to the lymph nodes. The presence of larger numbers of plasmacytoid cells in infected BALB/c mice, the more protracted infection of these cells, and their production of alpha interferon point to a complex and important role for the plasmacytoid cells in leishmaniasis.     

引流肺淋巴的淋巴结内灰尘颗粒的分布和结构变化

目的 :研究灰尘颗粒在引流肺淋巴的淋巴结内的分布和淋巴结的组织变化。方法 :取成人和儿童肺门淋巴结、气管支气管淋巴结和气管旁淋巴结 ,石蜡切片。取肺切除术患者的肺门淋巴结作超薄切片。结果 :尘细胞和灰尘颗粒分布于淋巴结被膜、淋巴窦和髓索内。肺门淋巴结和气管支气管淋巴结的光密度比气管旁淋巴结高 ,成人肺门淋巴结、气管支气管淋巴结和气管旁淋巴结的光密度高于儿童的淋巴结。成人淋巴结的血管密度与儿童淋巴结之间存在着显著性差异。间质胶原纤维增生。结论 :在引流肺淋巴的淋巴结内 ,肺门淋巴结和气管支气管淋巴结内的灰尘颗粒明显多于气管旁淋巴结 ,成人淋巴结灰尘颗粒比儿童多。在成人 ,灰尘颗粒引起淋巴结的淋巴组织减少 ,纤维组织和血管增生     

Cholesterol granulomas in lymph nodes draining a benign ovarian neoplasm

A 69-year-old woman underwent a hysterectomy and bilateral salpingo-oophorectomy for a 20-cm right ovarian tumor. Multiple peritoneal and lymph node biopsy specimens were obtained to determine the clinical stage. Despite the surgeon's concern of malignancy, pathologic examination demonstrated a benign mucinous cystadenoma. Periaortic and external iliac lymph nodes showed an unusual granulomatous reaction, with multinucleated giant cells surrounding cholesterol-like clefts. Analysis of cyst fluid from the ovarian tumor revealed high concentrations of protein and lipid; the lipid component was predominantly free cholesterol (0.61 mumole/mL) and phospholipid (0.225 mumole/mL). We speculate that fluid from the ovarian neoplasm drained into regional lymph nodes, causing this unusual granulomatous response.     

树突状细胞引流淋巴结归巢的研究进展

树突状细胞(dendritic cells,DCs)是目前已知的体内功能最强的专职性抗原提呈细胞(professional antigen-present-ing cells,pAPC),在引发和调节机体的免疫反应中起着重要作用。树突状细胞最重要的功能是摄取、加工处理、提呈抗原,并刺激初始T细胞(naive T cells)活化、增殖,从而激发机体的免疫应答。DCs这一功能是在体内迁移过程中发挥的,其中DCs归巢至引流淋巴结被认为是激发免疫应答的关键步骤之一。本文将就近年来DCs归巢至引流淋巴结的研究进展作一综述。     

乳腺癌原发灶及腋窝淋巴结中细胞毒性淋巴细胞与临床病理的关系

目的 分析乳腺癌原发灶组织和腋淋巴结中细胞毒性淋巴细胞的数量和状态,并与乳腺癌临床病理特征相比较,探讨其意义.方法 对资料齐全且术前均未接受任何化疗和放疗的74例乳腺癌原发灶及所切除的腋淋巴结进行病理分型及临床病理分期,并分为淋巴结无转移组和有转移组.采用免疫组织化学催化信号放大系统和EnVision法,通过单克隆抗体CD8、粒酶B、穿孔素、CD56的检测,分析肿瘤原发灶及腋淋巴结中细胞毒性淋巴细胞的表型和功能.结果 在肿瘤原发灶组织中CD8+细胞间质明显多于实质,淋巴结无转移组肿瘤局部[(35.7±16.0)个]及腋淋巴结CD8+细.胞数[(53.0±18.2)个]均高于淋巴结有转移组[(23.7±9.6)个和(38.2±12.7)个],肿瘤原发灶CD8+细胞数在5年生存组[(32.9±14.1)个]显著高于死亡组[(20.1±9.9)个].以粒酶B为细胞毒性淋巴细胞活化标记时,细胞毒性淋巴细胞的百分率差异无统计学意义;肿瘤组织和腋淋巴结中CD8+、CD56+细胞数均与临床病理分期无关.与Ⅰ期相比,在Ⅲ+Ⅳ期原发灶组织和腋淋巴结中细胞毒性淋巴细胞的数量显著降低.值得注意的是,在多数情况下,原发灶组织中穿孔素+细胞数量明显低于粒酶B+细胞.结论 在乳腺癌中细胞毒性淋巴细胞对抑制其肿瘤转移、提高患者生存率有一定意义.组织中细胞毒性淋巴细胞功能缺陷可能是影响其发挥抗瘤效应的重要因素.     

The lymph nodes draining the small intestine and colon are anatomically separate and immunologically distinct

Dendritic cells (DCs) in the small intestine (SI) and colon are fundamental to direct intestinal immune responses; they migrate to the mesenteric lymph nodes (MLNs) and prime T cells. We demonstrate anatomical segregation of lymphatic drainage from the intestine, specifically that DCs from the SI and colon migrate to different nodes within the MLN, here called the sMLN and cMLN. As a consequence, different frequencies of DC subsets observed in the SI and colon are reflected among the DCs in the sMLN and cMLN. Consistent with the SI's function in absorbing food, fed antigen is presented in the sMLN, but not in the cMLN. Furthermore, the levels of expression of CCR9 and α4β7 are increased on T cells in the sMLN compared with the cMLN. DCs from the cMLN and colon are unable to metabolize vitamin A to retinoic acid (RA); thus, DCs may contribute to the differential expression of tissue homing markers observed in the sMLN and cMLN. In summary, the sMLN and cMLN, and the DCs that migrate to these LNs are anatomically and immunologically separate. This segregation allows immune responses in the SI and colon to be controlled independently.     

Changes in lymphocyte accumulation and proliferation in the lymph nodes draining the pregnant uterus.

Changes in weight, lymphocyte accumulation and cellular proliferation have been measured in the lymph nodes draining the uterus during inter- and intra-strain pregnancies and compared with similar effects after other antigenic stimuli. From the data obtained it was concluded that "paternal" antigenic stimulation from the conceptus initiated an immune response in these nodes. The mechanisms of the subsequent suppression of this response are discussed.     

Taking the lymphatic route: dendritic cell migration to draining lymph nodes

In contrast to leukocyte migration through blood vessels, trafficking via lymphatic vessels (LVs) is much less well characterized. An important cell type migrating via this route is antigen-presenting dendritic cells (DCs), which are key for the induction of protective immunity as well as for the maintenance of immunological tolerance. In this review, we will summarize and discuss current knowledge of the cellular and molecular events that control DC migration from the skin towards, into, and within LVs, followed by DC arrival and migration in draining lymph nodes. Finally, we will discuss potential strategies to therapeutically target this migratory step to modulate immune responses.     

Modulation of IgE response and cytokine production in Peyer's patches and draining lymph nodes in sensitized mice made tolerant by oral dust mite administration.

Such allergic diseases as rhinitis and asthma are IgE-mediated type I reactions and are controlled primarily by Th2 cells. One of the major dust mites, Dermatophagoides pteronyssinus (Dp), is considered to cause allergic reactions. Oral tolerance, largely used to modulate immune response, opens the possibility of modulating Th2 allergic responses. We observed downmodulation of total and specific IgE antibody levels as well as the number of specific IgE-secreting cells with Dp feeding in previously sensitized mice. Analysis of the cytokine profile in mucosal lymphoid tissues in the protocol revealed altered patterns of interferon-gamma (IFN-gamma), interleukin-5 (IL-5), and transforming growth factor-beta (TGF-beta) secretion in Dp-fed animals. The results suggest that both the Th and B cell populations are modulated in mice made tolerant by oral Dp feeding. Understanding the mechanisms at the mucosal level that underlie oral tolerance can improve its use in allergy immunotherapy.     

Phenotypic characteristics of antigen-bearing cells in the draining lymph nodes of contact sensitized mice

Following contact sensitization of mice there is a rapid accumulation of dendritic cells (DC) within lymph nodes draining the site of exposure. Previous studies have revealed that cells bearing high levels of contact allergen can also be identified within the low buoyant density fraction of draining lymph node cells, and it has been assumed that the majority of these are DC. The purpose of the present study was to establish the phenotypic characteristics of the antigen-bearing cells which appear in lymph nodes within hours of skin painting with contact allergens, including the contact sensitizing fluorochromes fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RITC). Indirect immunofluorescence and two-colour immunofluorescence analyses revealed that initially all antigen-bearing cells which arrive in the draining lymph nodes express class II MHC antigens and exhibit a dendritic morphology. Phagocytic cells, cells reactive with F4/80 and anti-Mac-1 antibodies and lymphoblasts are not associated with detectable levels of antigen. In addition, although Thy-1+ cells co-fractionate with lymph node DC they are not dendritic in nature and are not associated with antigen. These data are compatible with the hypothesis that following skin sensitization epidermal Langerhans' cells bind antigen and transport it to the regional lymph nodes. In addition, it is clear that the recently described population of Thy-1+, Ia- dendritic cells within the murine epidermis do not perform a similar function.     

Leukocytes infiltrate the skin and draining lymph nodes in response to the protozoan Leishmania infantum chagasi

The vector-borne protozoan Leishmania infantum chagasi causes minimal inflammation after inoculation into skin but disseminates to cause fatal visceral leishmaniasis. To define the inflammatory response at the parasite inoculation site, we introduced metacyclic L. infantum chagasi promastigotes intradermally into BALB/c mouse ears and studied inflammatory cells over 7 days. Ly6G(+) neutrophils rapidly infiltrated the dermis, peaking after 6 to 24 h. Macrophages and NK cells next infiltrated the dermis, and NK followed by B cells expanded in draining lymph nodes. Parasite-containing phagocytes were tracked with fluorescent mCherry-labeled L. infantum chagasi. Ly6G(+) neutrophils contained the greatest proportion of intracellular parasites 6 to 24 h after inoculation, whereas dermal macrophages harbored the majority of intracellular parasites after 2 to 7 days. These observations were validated microscopically. Low doses of antibody transiently depleted mice of neutrophils, leaving other cells intact. Combined results of in vivo imaging, flow cytometry, and quantitative PCR showed that neutrophil depletion slowed the clearance of extracellular (luciferase-positive) promastigotes during the first 24 h after inoculation yet decreased the numbers of leukocytes containing intracellular (mCherry-positive) parasites. From 3 days onward, total L. infantum chagasi-containing dermal leukocytes and total L. infantum chagasi parasites in draining lymph nodes were similar in both groups. Nonetheless, a second wave of L. infantum chagasi-containing neutrophils occurred 7 days after parasite inoculation into neutrophil-depleted mice, corresponding to the time of neutrophil recovery. Thus, neutrophils were recruited to the dermis even late after inoculation, and L. infantum chagasi trafficked through neutrophils in both neutrophil-depleted and control mice, albeit with different kinetics. Recruitment of neutrophils and transient parasite residence in neutrophils may play a role in nonulcerative forms of leishmaniasis.     

The detection of hemagglutinins in regional lymph nodes following skin homotransplantation in rabbits

Summary Hemagglutinins were investigated in extracts of rabbit regional lymph nodes following homotransplantation of skin to the ears. The regional lymph node of the other ear of the same animal after simultaneous autotransplantation of the skin served as the control.In 19 of 36 rabbits antibodies were revealed in lymph node extracts; these antibodies were not present in the serum. The antibodies were detected in 9 controls, but their titre was lower than in the experimental animals. Thus, the author confirmed that antibodies are formed in the cells of rabbit regional lymph nodes in response to homotransplantation of skin.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 12, pp. 68–71, December, 1962