Elgueta Raul, Tobar Jaime A, Shoji Kenji F, De Calisto Jaime, Kalergis Alexis M, Bono Maria R, Rosemblatt Mario, Sáez Juan C
Universidad de Chile, Santiago, Chile.
J Immunol. 2009 Jul 1;183(1):277-84. doi: 10.4049/jimmunol.0801854.
The acquired immune response begins with Ag presentation by dendritic cells (DCs) to naive T cells in a heterocellular cell-cell contact-dependent process. Although both DCs and T cells are known to express connexin43, a gap junction protein subunit, the role of connexin43 on the initiation of T cell responses remains to be elucidated. In the present work, we report the formation of gap junctions between DCs and T cells and their role on T cell activation during Ag presentation by DCs. In cocultures of DCs and T cells, Lucifer yellow microinjected into DCs is transferred to adjacent transgenic CD4(+) T cells, only if the specific antigenic peptide was present at least during the first 24 h of cocultures. This dye transfer was sensitive to gap junction blockers, such as oleamide, and small peptides containing the extracellular loop sequences of conexin. Furthermore, in this system, gap junction blockers drastically reduced T cell activation as reflected by lower proliferation, CD69 expression, and IL-2 secretion. This lower T cell activation produced by gap junction blockers was not due to a lower expression of CD80, CD86, CD40, and MHC-II on DCs. Furthermore, gap junction blocker did not affect polyclonal activation of T cell induced with anti-CD3 plus anti-CD28 Abs in the absence of DCs. These results strongly suggest that functional gap junctions assemble at the interface between DCs and T cells during Ag presentation and that they play an essential role in T cell activation.
获得性免疫反应始于树突状细胞(DCs)以异细胞间细胞接触依赖的过程将抗原呈递给初始T细胞。虽然已知DCs和T细胞都表达连接蛋白43(一种间隙连接蛋白亚基),但连接蛋白43在T细胞反应起始中的作用仍有待阐明。在本研究中,我们报道了DCs和T细胞之间间隙连接的形成及其在DCs呈递抗原期间对T细胞活化的作用。在DCs和T细胞的共培养物中,只有在共培养的至少前24小时存在特异性抗原肽时,微注射到DCs中的荧光黄才会转移到相邻的转基因CD4(+) T细胞。这种染料转移对间隙连接阻滞剂(如油酰胺)和含有连接蛋白细胞外环序列的小肽敏感。此外,在该系统中,间隙连接阻滞剂显著降低了T细胞活化,这通过较低的增殖、CD69表达和IL-2分泌得以体现。间隙连接阻滞剂导致的这种较低的T细胞活化并非由于DCs上CD80、CD86、CD40和MHC-II的表达降低。此外,在没有DCs的情况下,间隙连接阻滞剂不影响用抗CD3加抗CD28抗体诱导的T细胞多克隆活化。这些结果强烈表明,在抗原呈递过程中,功能性间隙连接在DCs和T细胞之间的界面处组装,并且它们在T细胞活化中起重要作用。