Parra E, Wingren A G, Hedlund G, Björklund M, Sjögren H O, Kalland T, Sansom D, Dohlsten M
Wallenberg Laboratory, Department of Tumor Immunology, University of Lund, Sweden.
J Immunol. 1994 Sep 15;153(6):2479-87.
This study describes the distinct roles of B7 and LFA-3 in the regulation of T cell responses. Activation of CD4+ T cells with Chinese hamster ovary (CHO)-DR4/B7 and CHO-DR4/LFA-3 cells that present the superantigen staphylococcal enterotoxin A resulted in significant T cell proliferation and substantial production of TNF and IFN-gamma. Strong IL-2 production was recorded in B7-costimulated, but not LFA-3-costimulated, cultures. The presence of B7 induced a more vigorous and prolonged proliferative T cell response compared with LFA-3 costimulation. In contrast, LFA-3 was more efficient than B7 in mediating cell adhesion of CD4+ T cells. Costimulation with the CHO-DR4/B7/LFA-3 triple transfectant resulted in enhanced cell adhesion, proliferation, and cytokine production compared with either DR4/B7 or DR4/LFA-3 alone. Optimal production of IL-2 by naive and memory CD4+ T cells was seen only when cells were costimulated with B7, whereas IFN-gamma production was induced in memory cells by both LFA-3 and B7. The Jurkat T cell line responded to CHO-DR4/B7/LFA-3 in a manner similar to peripheral blood CD4+ T cells. Reverse transcriptase-PCR analysis of Jurkat cells stimulated with staphylococcal enterotoxin E and the different CHO transfectants revealed that the cooperative effect of B7 and LFA-3 on IL-2 production was also seen at the mRNA level. The large amounts of IL-2 produced by B7 costimulation indicate a paracrine function of the B7/CD28 pathway, whereas the LFA-3/CD2 pathway provides strong adhesion and may facilitate autocrine T cell expansion. Combined expression of the B7 and LFA-3 molecules seems to provide an optimal Ag-presenting function that ensures strong adhesion and optimal signal transduction.
本研究描述了B7和淋巴细胞功能相关抗原-3（LFA-3）在调节T细胞应答中的不同作用。用表达超抗原葡萄球菌肠毒素A的中国仓鼠卵巢（CHO）-DR4/B7和CHO-DR4/LFA-3细胞激活CD4⁺T细胞，导致显著的T细胞增殖以及大量肿瘤坏死因子（TNF）和γ干扰素（IFN-γ）的产生。在B7共刺激而非LFA-3共刺激的培养物中记录到强烈的白细胞介素-2（IL-2）产生。与LFA-3共刺激相比，B7的存在诱导了更强烈和持久的增殖性T细胞应答。相反，LFA-3在介导CD4⁺T细胞的细胞黏附方面比B7更有效。与单独的DR4/B7或DR4/LFA-3相比，用CHO-DR4/B7/LFA-3三重转染细胞进行共刺激导致细胞黏附、增殖和细胞因子产生增强。仅当细胞用B7共刺激时，幼稚和记忆CD4⁺T细胞才能产生最佳水平的IL-2，而LFA-3和B7均可诱导记忆细胞产生IFN-γ。Jurkat T细胞系对CHO-DR4/B7/LFA-3的反应方式与外周血CD4⁺T细胞相似。用葡萄球菌肠毒素E和不同的CHO转染细胞刺激Jurkat细胞后进行逆转录聚合酶链反应（RT-PCR）分析表明，B7和LFA-3对IL-2产生的协同作用在mRNA水平也可见。B7共刺激产生的大量IL-2表明B7/CD28途径具有旁分泌功能，而LFA-3/CD2途径提供强大的黏附作用并可能促进自分泌T细胞扩增。B7和LFA-3分子的联合表达似乎提供了最佳的抗原呈递功能，可确保强大的黏附作用和最佳的信号转导。
