The interaction defect of accessory molecules is responsible for the poor ex vivo response to human antigens of mouse T helper cells.
Mouse T cells fail to respond to xenogeneic pig and human antigens using the direct antigen-presenting pathway. The poor response by mouse CD8 cells is because of multiple defects in the molecular interactions between mouse CD8 cells and xenogeneic antigen-presenting cells (APCs). Using human CD4/DR3+, mouse CD4-/major histocompatibility complex (MHC) class II - mice, we investigated the defects in molecular interaction responsible for the poor response to xenogeneic antigens by naïve mouse CD4+ cells. Mouse CD4 cells failed to respond to human leucocyte antigen (HLA)-DR3 expressed on mouse APCs but developed a strong response to alloantigens, indicating a defect in the interaction between mouse CD4 and HLA-DR3 molecules. Human CD4+/mouse CD4- mouse T cells respond poorly to human and pig APCs but not allogeneic APCs, indicating that accessory molecular interactions are deficient across highly separated species. Adding mouse interleukin-2 (IL-2) to the mixed lymphocyte reaction system did not improve the poor response to human or pig antigens by mouse or human CD4+/mouse CD4- mouse T cells. Therefore, multiple molecular interactions deficient between mouse CD4 cells and human or pig APCs may lead to the poor response to xenogeneic antigens by naïve mouse CD4 cells.
Sun
Y
Y
Department of Surgery, University of Nebraska Medical Center, The Lied Transplant Center, Omaha, NE 68198, USA.
Langnas
A N
AN
Zhao
Y
Y
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013552:Swine
D000941:Antigens; D000949:Histocompatibility Antigens Class II