EXPRESSION OF IL-10R ON LYMPH NODES AND SPLEEN CELLS OF BORRELIA-INFECTED MICE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们以前报道，促炎细胞因子干扰素-γ（IFN-？）和白细胞介素-6（IL-6），响应于脂化的外表面蛋白A（L-OspA）和合成的脂六肽Pam 3Cys，更有效地抑制抗炎细胞因子IL-10的淋巴结（LN）细胞的疾病抗性C57 BL/6 J比那些疾病易感的C3 H/HeJ小鼠。与C3 H小鼠相比，IL-10有效下调C57小鼠LN细胞中这些细胞因子的能力与C57小鼠LN中携带IL-10受体（IL-10 R）的细胞表达显着多于C3 H小鼠相关。相反，脾细胞从两个品系的小鼠表现出类似的水平IL-10 R轴承细胞，与IL-10的能力，以抑制生产IFN-？和IL-6在两种品系小鼠的脾细胞培养物中具有相同的效率。在这项研究中，我们研究了LN细胞中的特异性淋巴细胞群，这可能是IL-10抑制小鼠促炎细胞因子的靶点。在用B感染C3 H和C57小鼠一周后，离体获得LN和脾细胞。Burgdorferi感染，并通过流式细胞术评估CD 3 + CD 4+、CD 8+和CD 19+淋巴细胞上的IL-10 R表达。在来自C3 H和C57小鼠的LN和脾细胞中，大多数携带IL-10 R的细胞具有CD 19+表型（B细胞）。然而，来自C3 H小鼠的CD 19+细胞比C57小鼠表达更多的IL-10 R，这表明CD 19+细胞最有可能不是IL-10下调促炎细胞因子的靶标，因为IL-10抑制C57小鼠LN细胞中促炎细胞因子的效率更高。CD 3+、CD 4+和CD 8 + T淋巴细胞均不表达显著百分比的IL-10 R。这些发现可能表明，其他IL-10 R轴承细胞，如巨噬细胞或树突状细胞可能是IL-10抑制炎症细胞因子的LN和莱姆病小鼠脾脏的目标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We previously reported that the proinflammatory cytokines interferon-gamma (IFN-?) and interleukin-6 (IL-6), produced in response to lipidated outer surface protein A (L-OspA) and the synthetic lipohexapeptide Pam3Cys, were more efficiently inhibited by the anti-inflammatory cytokine IL-10 in lymph node (LN) cells of disease-resistant C57BL/6J than in those of disease-susceptible C3H/HeJ mice. The ability of IL-10 to efficiently down-modulate these cytokines in LN cells of C57 mice as compared with those of C3H mice correlated with the expression of significantly more IL-10 receptor (IL-10R)-bearing cells in LN of C57 than in those of C3H mice. On the contrary, spleen cells from both strains of mice showed similar levels of IL-10R bearing cells, correlating with the ability of IL-10 to dampen the production of IFN-? and IL-6 with the same efficiency in spleen cell cultures of both strains of mice. In this study, we investigated the specific lymphocyte population in LN cells that may be the target of IL-10 inhibition of proinflammatory cytokines in mice. LN and spleen cells were obtained ex vivo after one-week of infection of C3H and C57 mice with B. burgdorferi and assessed for IL-10R expression on CD3+ CD4+, CD8+ and CD19+ lymphocytes by flow cytometry. The majority of IL-10R bearing cells were of the CD19+ phenotype (B cells) in LN and spleen cells from C3H and C57 mice. However, CD19+ cells from C3H mice expressed more IL-10R than those of C57 mice, suggesting that CD19+ cells are most likely not the targets of IL-10 down-modulation of proinflammatory cytokines, given the greater efficiency by which IL-10 inhibits proinflammatory cytokines in LN cells of C57 mice. Neither CD3+, CD4+ nor CD8+ T lymphocytes expressed a significant percentage of IL-10R. These findings may suggest that other IL-10R bearing cells such as macrophages or dendritic cells may be targets of IL-10 inhibition of inflammatory cytokines in the LN and spleen of mice with Lyme disease.