Elevated major histocompatibility complex class I expression protects T cells from antibody- and macrophage-mediated deletion.
Macrophages are capable of destroying T cells with which they form cellular conjugates. The deletion can be prevented by the simultaneous transmission of costimulatory signals. We show here that T cells with elevated major histocompatibility complex (MHC) class I expression are resistant against macrophage-mediated cytotoxicity. T cells that express the CD45RO isotype, considered memory T cells, exhibit MHC class I antigen at higher density than naive CD45RA T cells and upregulate MHC class I expression promptly when they form cellular conjugates with macrophages. We confirm previous observations that CD45RA T cells are more susceptible to antibody- and macrophage-mediated deletion than memory CD45RO T cells. When MHC class I molecules are masked by specific monoclonal antibody or antibody Fab fragments, CD45RA T cells and CD45RO T cells exhibit equal susceptibility to macrophage cytotoxicity, demonstrating that the difference between CD45RA and CD45RO T cells in their sensitivity to macrophage cytotoxicity is determined by their MHC I expression. Separation of CD4 T cells from CD8 T cells deprives memory CD4 T cells of their resistance against macrophage cytotoxicity, suggesting that memory T cells' resistance against destruction by macrophages is controlled by regulatory T cells.
Orlikowsky
T
T
New York Medical College, Department of Microbiology & Immunology, Valhalla, NY, 10595, USA.
Wang
Z
Z
Dudhane
A
A
Mittler
R
R
Trejo
V
V
Dannecker
G E
GE
Niethammer
D
D
Hoffmann
M K
MK
D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D018929:Cell Culture Techniques; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D017493:Leukocyte Common Antigens / Q000032:analysis; D008264:Macrophages / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D017493:Leukocyte Common Antigens