研究Galectins在Treg-of-B2細胞的調控機轉上所扮演的角色

Abstract

Treg細胞有抑制免疫反應的功能，在免疫系統中扮演重要角色。過去研究指出，當CD4+ T細胞受到細胞激素刺激時，可以轉變為CD4+ CD25+ T細胞，並且有免疫抑制功能，稱作為iTreg細胞。最近我們的研究發現，以B2細胞作為抗原呈獻細胞可以誘導CD4+ T細胞成為類似Treg的細胞，我們稱之為Treg-of-B2細胞，而對於Treg-of-B2細胞的免疫抑制機轉目前並不清楚。動物凝集素家族中的半乳糖凝集素是最近免疫研究上一個重要的議題，目前發現了15種的半乳糖凝集素，但大部分的功能並不清楚。半乳糖凝集素在免疫細胞中參與了許多反應，例如半乳糖凝集素-2可以誘發CD8+ T細胞的細胞凋亡，但是半乳糖凝集素-3反而是抑制細胞凋亡的發生。本研究探討半乳糖凝集素在Treg-of-B2細胞的免疫抑制中的影響，首先收集活化的Treg-of-B2細胞，分析半乳糖凝集素的RNA表現，結果發現半乳糖凝集素-2有高量的表現，並且同時也可以在細胞培養液中測到半乳糖凝集素-2的表現。本次研究也同時分析Tr1細胞的半乳糖凝集素RNA表現，但並沒有任何表現。接著發現Treg-of-B2細胞執行免疫抑制功能時，不一定需要細胞接觸，在加入乳糖阻礙半乳糖凝集素作用，發現Treg-of-B2細胞的免疫抑制功能有顯著的下降。CD4+ T細胞的增生實驗中加入半乳糖凝集素-2發現半乳糖凝集素-2可抑制CD4+ T細胞的增生，因此透過本次研究可知半乳糖凝集素-2參與在Treg-of-B2細胞的免疫抑制功能中。

Regulatory T cells (Treg cells) have an ability to suppress immune response. Under particular condition, naive CD4+ T cell could differentiate into inducible Treg (iTreg) cells with regulatory functions. In the past few years, some in vitro experiments have shown that splenic B220+ B2 cells could convert naive CD4+ T cells into induced Treg cells (referred to as Treg-of-B2 cells). Treg-of-B2 cells had immune suppressive ability like nTreg cells, but the mechanism remained unclear. To date, 15 galectins have been identified in mammals, only galectin-1, -2, -3, -4, -7, -8, -9, -12 identified in mice. Recent studies have shown that several galectins (including galectin-1, -2, -3, -7, -8, -9, and -12) induced apoptosis in T cell. Galectin-1 was a key effector molecule in the regulation function of CD4+CD25+ T cells. Galectin-2 induced activated CD8+ T cells apoptosis. Galectin-3 exerted several functions such as inhibition of apoptosis, promotion of cell growth, and regulation of TCR signaling. The aim of our study was to investigate the relationship between galectins and the regulatory function of Treg-of-B cells. First, expression profile of galectins in activated Treg-of-B2 cells and activated Tr1 cells had been screened. We found that activated Treg-of-B2 cells had higher galectin-2 expression but Tr1 cells did not. Second, the suppressive function of Treg-of-B2 cells did not need cell-cell contact. By adding lactose and transwell system in suppressive assay, we found that galectin-2 might be a factor in the function of Treg-of-B2 cells. We confirmed the role of galectin-2 in the proliferation of CD4+ CD25- T cells by adding recombinant galectin-2 in culture medium and we found that the proliferation of CD4+ CD25- T cells was decreased. Our finding clarify that a part of suppressive ability of Treg-of-B2 cells was galectin-2 secretion.