Mani Rajesh, Mercier Corinne, Delauw Marie-France, Suzuki Yasuhiro
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY40536, USA.
CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, Universite Grenoble Alpes, Grenoble, France.
Microbes Infect. 2023 Nov-Dec;25(8):105182. doi: 10.1016/j.micinf.2023.105182. Epub 2023 Jul 8.
CD8 T cells from HLA-A2.1-transgenic mice, but not wild-type mice, immunized with the amino-terminus region (aa 41-152) of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii secreted large amounts of perforin and granzyme B in response to GRA6Nt through antigen presentation by HLA-A2.1 in vitro. When those CD8 T cells were transferred into chronically infected HLA-A2.1-expressing NSG mice deficient in T cells, cerebral cyst burden of the recipients of HLA-A2.1-transgenic T cells, but not of WT T cells, became significantly less than that of control mice with no cell transfer. Furthermore, the significant reduction of the cyst burden by a transfer of the HLA-A2.1-transgenic CD8 immune T cells required an expression of HLA-A2.1 in the recipient NSG mice. Thus, antigen presentation of GRA6Nt by human HLA-A2.1is able to activate anti-cyst CD8 T cells that eliminate T. gondii cysts through antigen presentation by human HLA-A2.1.
用刚地弓形虫致密颗粒蛋白6（GRA6）的氨基末端区域（氨基酸41 - 152）免疫的HLA - A2.1转基因小鼠的CD8 T细胞，而非野生型小鼠的CD8 T细胞，在体外通过HLA - A2.1的抗原呈递，对GRA6Nt产生应答，分泌大量穿孔素和颗粒酶B。当将这些CD8 T细胞转移到慢性感染且缺乏T细胞的表达HLA - A2.1的NSG小鼠中时，接受HLA - A2.1转基因T细胞的小鼠的脑囊肿负荷显著低于未进行细胞转移的对照小鼠，而接受野生型T细胞的小鼠则不然。此外，通过转移HLA - A2.1转基因CD8免疫T细胞使囊肿负荷显著降低，这需要受体NSG小鼠表达HLA - A2.1。因此，人HLA - A2.1对GRA6Nt的抗原呈递能够激活抗囊肿CD8 T细胞，这些细胞通过人HLA - A2.1的抗原呈递消除刚地弓形虫囊肿。
