The CD44 variant isoforms CD44v6 and CD44v7 are expressed by distinct leukocyte subpopulations and exert non-overlapping functional activities
The CD44 variant isoforms CD44v6 and CD44v7 are expressed by distinct leukocyte subpopulations and exert non-overlapping functional activities
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DOI：
10.1093/intimm/12.1.37
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发表时间：
2000-01-01
影响因子：
4.4
通讯作者：
Zöller, M
中科院分区：
文献类型：
--
作者：
Seiter, S;Schmidt, DS;Zöller, M
我们最近描述了抗CD 44 s、抗CD 44 v6和抗CD 44 v7干扰迟发型超敏反应（DTH）。然而，TNBS诱导的结肠炎只能通过抗CD 44 v7治愈。为了阐明CD 44 v6和CD 44 v7的不同功能活性的机制，我们探讨了它们在体内和体外对淋巴细胞活化的贡献。CD 44 v6和CD 44 v7在活化的淋巴细胞亚群上明显表达。CD 44 v6的表达主要限于T细胞母细胞。在CD 4（+）细胞、B细胞和单核细胞上检测到CD 44 v7。在抗CD 44 v6和抗CD 44 v7的存在下，体外淋巴细胞的促有丝分裂和抗原刺激受损。因此，抗CD 44 v6和抗CD 44 v7减轻了2，4-dlnitro-1-fluorobenzene致敏和攻击小鼠的DTH反应。然而，CD 44 v6和CD 44 v7特异性抗体的看似相似的作用是由不同的活性引起的。抗CD 44 v6治疗导致主要由CD 8（+）细胞产生的IL-2和IFN-γ的下调。在抗CD 44 v7处理的小鼠中，IL-12的表达降低。IL-10水平的升高伴随着这种降低。后者是由于抗CD 44 v7介导的CD 4+细胞和单核细胞之间相互作用的阻断以及B细胞的主动触发。因此，抗CD 44 v7和antiD 44 v7在非常特定的点干扰淋巴细胞活化。CD 44 v6主要在T细胞水平发挥作用。CD 44 v7影响B细胞产生促炎细胞因子以及CD 4（+）细胞和抗原呈递细胞之间的相互作用。由于CD 44同种型在胞浆内尾区没有差异，因此不同的活性必须由不同白细胞亚群上的表达以及与不同配体的相互作用产生。
We have described recently that anti-CD44s, anti-cD44v6 and anti-CD44v7 interfere with delayed-type hypersensitivity (DTH) reactions. Yet, TNBS-induced colitis can be cured only by anti-CD44v7. To clarify the mechanisms underlying the divergent functional activities of CD44v6 and CD44v7 we explored their contribution to lymphocyte activation in vivo and in vitro. CD44v6 and CD44v7 are distinctly expressed on subpopulations of activated lymphocytes. Expression of CD44v6 is mainly restricted to T cell blasts. CD44v7 has been detected on CD4(+) cells, B cells and monocytes. Mitogenic and antigenic stimulation of lymphocytes in vitro was impaired in the presence of anti-CD44v6 and anti-CD44v7. Accordingly, anti-CD44v6 and anti-CD44v7 mitigated the DTH reaction in 2,4-dlnitro-1-fluorobenzene-sensitized and challenged mice. However, the seemingly similar effects of CD44v6- and CD44v7-specific antibodies resulted from different activities. Anti-CD44v6 treatment led to a down-regulation of IL-2 and IFN-gamma production predominantly by CD8(+) cells. In anti-CD44v7-treated mice expression of IL-12 was decreased. Elevated levels of IL-10 accompanied this reduction. The latter resulted from an anti-CD44v7-mediated blockade of interactions between CD4+ cells and monocytes as well as an active triggering of B cells. Thus, anti-CD44v7 and anticD44v7 interfere with lymphocyte activation at very specific points. CD44v6 functions predominantly at the T cell level. CD44v7 influences production of proinflammatory cytokines by B cells as well as an interaction between CD4(+) cells and antigen-presenting cells. As CD44 isoforms do not differ in their intracytoplasmatic tail, the distinct activities must result from expression on different leukocyte subsets and interactions with distinct ligands.