Cutaneous immunization rapidly activates liver invariant Valpha14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity.

Cutaneous immunization rapidly activates liver invariant Valpha14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity.
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DOI:
10.1084/jem.20021562
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发表时间:
2003-12-15
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Askenase PW
Askenase PW
中科院分区:
其他
文献类型:
--
作者:
Campos RA;Szczepanik M;Itakura A;Akahira-Azuma M;Sidobre S;Kronenberg M;Askenase PW

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为了引起接触敏感性(CS),T细胞募集需要一个由B-1细胞介导的CS启动过程,B-1细胞产生IgM,激活补体促进T细胞进入组织。我们现在证明,Vα14i NKT细胞可能通过在免疫后早期释放IL-4来诱导B-1细胞激活。在Jα18−/−和CD1d−/−NKT细胞缺陷小鼠中,CS启动过程缺失,并由富含Vα14i NKT细胞的群体重组。如果细胞来自IL-4−/−小鼠,转移是无效的。特异性四聚体直接染色显示,免疫后30min,肝V-α-14i-NKT细胞数量增加,免疫后2小时细胞数量增加近一倍。免疫B-1细胞的转移也重建了NKT细胞缺陷小鼠的CS反应。B-1细胞作用于Vα14i NKT细胞的下游,以恢复CS的起始。此外,系统地给予Jα18−/−或CD1d−/−NKT细胞缺陷小鼠的IL-4重建了CS的诱导。此外,与致敏的WT小鼠相比,免疫Jα18−/−小鼠的脾细胞产生更少的抗原(Ag)特异性免疫球蛋白M抗体。综上所述,这些发现表明,皮肤免疫后非常早的时候,Vα14i NKT细胞被刺激产生IL-4,IL-4激活B-1细胞产生抗原特异性IgM,随后需要招募效应性T细胞来激发CS反应。
T cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated by B-1 cells that produce IgM, which activates complement to promote T cell passage into the tissues. We now show that Vα14i NKT cells induce B-1 cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/− NKT cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT cells. Transfers are not effective if cells are derived from IL-4−/− mice. Staining with specific tetramers directly showed that hepatic Vα14i NKT cells increase by 30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 cells also reconstitutes CS responses in NKT cell–deficient mice. The B-1 cells act downstream of the Vα14i NKT cells to restore CS initiation. In addition, IL-4 given systemically to Jα18−/− or CD1d−/− NKT cell–deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jα18−/− mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Vα14i NKT cells are stimulated to produce IL-4, which activates B-1 cells to produce Ag-specific IgM, subsequently needed to recruit effector T cells for elicitation of CS responses.
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