VMIP-II for inducing dephosphorylation of CD8<+> T cells to form Tcm and application of vMIP-II in medicines

Abstract

The invention discloses application of virus macrophage inflammatory protein vMIP-II for inducing dephosphorylation of CD8<+> T cells to form Tcm. The vMIP-II for inducing dephosphorylation of the CD8<+> T cells to form the Tcm is developed in a laboratory and is verified by the National Institute for Control of Pharmaceutical and Biological Products. According to the invention, the CD8<+> T cellsare researched through a rhesus SIV infection model. The research finds that: the vMIP-II can enable Tcm to be proliferated depending on the dosage of the vMIP-II, and the differential gene of the proliferative cell is mainly enriched in a chemokine receptor and a phosphorylation pathway. The research further finds that: the proliferation is as follows: the vMIP-II closes a CD8<+> T chemokine receptor, promotes low expression of G protein, reduces the concentration of intracellular Ca<2+> and mitochondrial membrane potential, inhibits phosphorylation related genes, and promotes low expressionof phosphorylated proteins ERK1 / 2 and Akt, so that a CD8<+> T phosphorylation signal is weakened, metabolic reprogramming is carried out, and the CD8<+> T is converted into the Tcm. Therefore, the discovery of the vMIP-II action mechanism provides a brand-new strategy for drug research and development of HIV / SIV infected AIDS, provides a new means for adoptive immunotherapy of virus resistance and tumor resistance, and has important clinical application value.

Description

technical field [0001] The present invention belongs to the basic research field of viral macrophage inflammatory protein vMIP-II in the prevention and treatment of inflammation and SIV / HIV infection. More specifically, the invention relates to the induction of CD8 by viral macrophage inflammatory protein vMIP. + Dephosphorylation of T cells into long-lived central memory cells (CD8 + Tcm) mechanism of action. Background technique [0002] Memory CD8 that circulates in blood and resides in lymphoid organs + T cells are an important component of long-lived T cell immunity. This is due to CD8 + T cells are mainly activated by recognizing antigenic peptides presented by MHC I molecules through the T cell receptor (TCR) on their surface, and activated CD8 + 90%~95% of T cells will be apoptotic during the contraction phase, and only a small part will form antigen-specific memory CD8 + T cells. memory CD8 + T cells remain capable of rapid effector clearance of antige...

AI Technical Summary

Problems solved by technology

But how does recombinant vMIP-II inhibit virus entry into target cells, how does it promote CD8 + Molecular mechanism of T cell proliferation remains unclear

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