Studying The Function Of Tespa1 In T Cell By Bone Marrow Reconstitution Model And Listeria Infection Model

T cells are an important member of the acquired immune system,T cells play an important role in anti-infection immunity,antitumor immunity and in autoimmune diseases.After completion of T cells in the thymus to complete its development,T cells function in peripheral immune organs,behind this involves a series of complicated regulatory mechanism.Clarifying the molecular mechanism of T cells in the development process and the immune response in peripheral immune organs is important for us to provide immune intervention targets for clinical anti-infection and tumor immunotherapy.In recent years,researchers have found that some new molecules play an important role in the development of T cells in the thymus,Tespal is one of the molecules reported in recent years,Tespal plays an important role in T cell development.Tespal deficiency resulted in failure of the positive selection of thymocytes,which reflected impaired thymocyte development.But the key structure of the domain of Tespal remains unclear.We verified Tespal deficiency resulted in impaired thymocyte development by bone marrow reconstitution model.Rescue Tespal of hematopoietic stem cells can restore T cell development and the percentage of peripheral T cells.We also mutated two amino acids residues in Tespal(Phe187 and Phe188).The study found that there was no obvious difference in the percentage of T cells,but the number of T cells in thymus and peripheral lymphoid organs decreased obviously after the mutation of Tespal,prompting that two amino acids residues in Tespal(Phel 87 and Phe188)might affect thymocyte development.In order to further study the function of Tespal in T cells of peripheral lymphoid organs,we used Listeria infection in Tespal-/-mice.Listeria monocytogenes is a saprophytic gram positive bacterium.The main media of Listeria monocytogenes is food,it is one of the most deadly foodborne pathogens.Due to Listeria monocytogenes is a kind of intracellular parasitic bacteria,Listeria monocytogenes is cleared mainly by cellular immunity,Listeria monocytogenes can serve as a kind of pattern of pathogens used to study antigen specific memory CD8+ T cell reaction.In order to study the role of Tespal in the process of host resistance to pathogen infection,we used Listeria infection in wild type mice and Tespal-/-mice.We analyzed CD8+ T cell activation,cytokines of CD8+ T cells,as well as the specific CD8+ T cell differentiation in the process of the primary immune response.The results showed that Tespal deficiency would lead to higher percentage of CD8+ T cell activation of lymph node,but the secretion of cytokines and the formation of antigen specific CD8+ T cells were not been affected after Listeria infection.Through the detection of the ability of bacterial clearance in mice,the results showed that Tespal deficiency would not affect the ability to elimination of pathogen.Therefore Tespal deficiency had little effect on the primary immune response of Listeria infection.Above all,Tespal deficiency resulted in impaired thymocyte development.Further research showed that two amino acids residues in Tespal(Phe187 and Phe188)might affect thymocyte development.Tespal deficiency would lead to higher percentage of CD8+ T cell activation,but the secretion of cytokines,the formation of antigen specific CD8+ T cells and the ability of bacterial clearance were not been affected.