Exogenous and endogenous antigens are differentially presented by mast cells to CD4(+) T lymphocytes
Exogenous and endogenous antigens are differentially presented by mast cells to CD4(+) T lymphocytes
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DOI：
10.1002/eji.1830261036
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发表时间：
1996-10-01
影响因子：
5.4
通讯作者：
Mecheri, S
中科院分区：
文献类型：
--
作者：
Frandji, P;Tkaczyk, C;Mecheri, S
在本研究中，我们探讨了骨髓源性肥大细胞（BMMC）抗原呈递细胞（APC）功能的细胞因子依赖性调节，以及共刺激需求，并分析了抗原呈递到T细胞的性质。我们观察到粒细胞/巨噬细胞集落刺激因子（GM-CSF）诱导肥大细胞APC功能上调，而干扰素(IFN)- γ完全消除了APC功能。肥大细胞激活纯化淋巴结源性T细胞的能力提示了共刺激分子CD80和CD86的表达。事实上，融合蛋白mCTLA4-Ig的加入强烈抑制了肥大细胞对正常T细胞和T细胞杂交瘤3DO-54.8的抗原呈递。通过检测肥大细胞中CD80和CD86转录物，探讨GM-CSF和ifn - γ对APC功能的调控机制。gm - csf处理的肥大细胞显示CD80和CD86转录物的表达强烈增加，而在ifn - γ处理的肥大细胞中，这种表达完全消失。因此，GM-CSF和ifn - γ对CD80和CD86表达的上调和下调与APC功能直接相关。此外，我们还分析了内源性自身抗原的肥大细胞的抗原呈递。在原发性混合淋巴细胞反应（MLR）中，肥大细胞不能激活抗i- a或抗i- e特异性T细胞杂交瘤和同种异体反应性T细胞。此外，肥大细胞不呈现在B细胞上组成性表达的小鼠β 2-微球蛋白（m β 2-m）肽25-40。然而，肥大细胞，特别是那些用GM-CSF处理的肥大细胞，在外源肽存在下激活了抗m β 2-m特异性T细胞杂交瘤。小淋巴细胞刺激抗原-1 Mls-1(a)是一种由小鼠乳腺肿瘤原病毒-7 （MMTV-7）编码的病毒超抗原（vSAG）。肥大细胞，尽管在细胞表面存在一定量的主要组织相容性复合体II类，并且存在预测编码vSAG的MMTV转录本，但不能在体内或体外刺激Mls-1特异性的V β 6(+) T细胞(a)。相反，肥大细胞可以向特异性V β 8(+) T细胞呈递外源性细菌SAG，葡萄球菌肠毒素B （SEE）。肥大细胞对外源抗原的选择性呈递能力可能与肥大细胞通过区分自身和非自身参与免疫应答调节机制具有生理相关性。
In the present work, we explored the cytokine-dependent regulation of bone marrow-derived mast cell (BMMC) antigen-presenting cell (APC) function, and co-stimulation requirements, and analyzed the nature of antigens presented to T cells. We observed an up-regulation of the APC function of mast cells induced by granulocyte/macrophage-colony-stimulating factor (GM-CSF) and a complete abrogation by interferon (IFN)-gamma. Expression of co-stimulatory molecules CD80 and CD86 was suggested by the ability of mast cells to activate purified lymph node-derived T cells. Indeed, addition of the fusion protein mCTLA4-Ig strongly inhibited antigen presentation by mast cells to normal T cells and to the T cell hybridoma 3DO-54.8. The regulatory mechanisms of APC function by GM-CSF and IFN-gamma were investigated by measuring CD80 and CD86 transcripts in mast cells. GM-CSF-treated mast cells showed a strong increase in the expression of both CD80 and CD86 transcripts, whereas in IFN-gamma-treated mast cells, this expression was completely abrogated. Thus, up- and down-regulation of CD80 and CD86 expression by GM-CSF and IFN-gamma is directly correlated to the APC function. In addition, we analyzed antigen presentation by mast cells of endogenous self-antigens. Mast cells failed to activate anti-I-A or anti-I-E-specific T cell hybridomas and alloreactive T cells in primary mixed lymphocyte reactions (MLR). Furthermore, mast cells did not present the mouse beta 2-microglobulin (m beta 2-m) peptide 25-40, constitutively expressed on B cells. However, mast cells, especially those treated with GM-CSF, activated an anti-m beta 2-m-specific T cell hybridoma in the presence of exogenous peptide. The minor lymphocyte-stimulating antigen-1 Mls-1(a) is a viral superantigen (vSAG) encoded by the the mouse mammary tumor provirus-7 (MMTV-7). Mast cells, despite a reasonable amount of major histocompatibility complex class II on the cell surface and the presence of MMTV transcripts predicted to encode the vSAG, cannot stimulate in vivo or in vitro V beta 6(+) T cells specific for Mls-1(a). In contrast, mast cells could present the exogenous bacterial SAG, staphylococcal enterotoxin B (SEE), to specific V beta 8(+) T cells. The selective ability of mast cells to present exogenous antigens may have physiological relevance in that mast cells could participate in immune response regulatory mechanisms by discriminating self from nonself.