MIP-1α and MIP-1β differentially mediate mucosal and systemic adaptive immunity
MIP-1α and MIP-1β differentially mediate mucosal and systemic adaptive immunity
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DOI：
10.1182/blood-2002-07-2305
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发表时间：
2003-02-01
期刊：
影响因子：
20.3
通讯作者：
McGhee, JR
中科院分区：
文献类型：
--
作者：
Lillard, JW;Singh, UP;McGhee, JR
巨噬细胞炎性蛋白-1 α（MIP-1 α）和MIP-1 β是不同的但高度同源的CC趋化因子，其由多种宿主细胞响应于各种外部刺激而产生，并且共享对CCR 5的亲和力。为了更好地阐明这些CC趋化因子在获得性免疫中的作用，我们已经表征。MIP-1 α和MIP-1 β对细胞和体液免疫应答的影响。MIP-1 β刺激强的抗原（Ag）特异性血清免疫球蛋白G（IgG）和IgM应答，而MIP-1 β促进较低的IgG和IgM但较高的血清伊加和IgE抗体（Ab）应答。MO-1 ot升高Ag特异性IgG 1和IgG 2b，随后是IgG 2a和IgG 3亚类反应，而MIP-1 β仅刺激IgG 1和IgG 2b亚类。相应地，与MIP-1 α相比，MIP-1 β产生更高的Ag特异性粘膜分泌型伊加Ab滴度。MIP-1 α或MIP-1 β处理小鼠的脾T细胞显示出比对照组T细胞更高的Ag特异性Th 1（干扰素-γ [IFN-γ]）以及选择性Th 2（白细胞介素-5 [IL-5]和IL-6）细胞因子应答。有趣的是，与MIP-1 α治疗的小鼠相比，MIP-10治疗的小鼠的粘膜来源的T细胞显示出更高水平的IL-4和IL-6。然而，MIP-1 alpha有效地增强了抗原特异性细胞介导的免疫反应。与它们对体液和细胞免疫应答的选择性作用相关，这些趋化因子还以剂量依赖性方式差异性地吸引CD 4（+）与CD 8（+）T细胞并调节B220（+）细胞表达的CD 40、CD 80和CD 86以及CD 4（+）和CD 8（+）T细胞表达的CD 28、4-1BB和gp 39。总之，这些研究表明，这些CC趋化因子差异增强粘膜和血清体液以及细胞免疫应答。(C)2003年，美国血液学会。
Macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta are distinct but highly homologous CC chemokines produced by a variety of host cells in response to various external stimuli and share affinity for CCR5. To better elucidate the role of these CC chemokines in adaptive immunity, we have characterized. the affects of MIP-1alpha and MIP-1beta on cellular and humoral immune responses. MIP-1beta Stimulated strong antigen (Ag)-specific serum immunoglobulin G (IgG) and IgM responses, while MIP-1beta promoted lower IgG and IgM but higher serum IgA and IgE antibody (Ab) responses. MO-1ot elevated Ag-specific IgG1 and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1beta only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1beta produced higher, titers of Ag-specific mucosal secretory IgA Ab levels when compared with MIP-1alpha. Splenic T cells from MIP-1alpha- or MIP-1beta-treated mice displayed higher Ag-specific Th1 (interferon-gamma [IFN-gamma]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-10-treated mice displayed higher levels of IL-4 and IL-6 compared with MIP-1alpha-treated mice. However, MIP-1alpha effectively enhanced Ag-specific cell-mediated immune responses. In correlation with their selective effects on humoral and cellular immune responses, these chemokines also differentially attract CD4(+) versus CD8(+) T cells and modulate CD40, CD80, and CD86 expressed by B220(+) cells as well as CD28, 4-1BB, and gp39 expression by CD4(+) and CD8(+) T cells in a dose-dependent fashion. Taken together, these studies suggest that these CC chemokines differentially enhance mucosal and serum humoral as well as cellular immune responses. (C) 2003 by The American Society of Hematology.