ELEVATED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION PROTECTST-CELLS FROM ANTIBODY-MEDIATED AND MACROPHAGE-MEDIATED DELETION

Macrophages are capable of destroying T cells with which they form cel lular conjugates. The deletion can be prevented by the simultaneous tr ansmission of costimulatory signals. We show here that T cells with el evated major histocompatibility complex (MHC) class I expression are r esistant against macrophage-mediated cytotoxicity. T cells that expres s the CD45RO isotype, considered memory T cells, exhibit MHC class I a ntigen at higher density than naive CD45RA T cells and upregulate MHC class I expression promptly when they form cellular conjugates with ma crophages. We confirm previous observations that CD45RA T cells are mo re susceptible to antibody- and macrophage-mediated deletion than memo ry CD45RO T cells. When MHC class I molecules are masked by specific m onoclonal antibody or antibody Fab fragments, CD45RA T cells and CD45R O T cells exhibit equal susceptibility to macrophage cytotoxicity, dem onstrating that the difference between CD45RA and CD45RO T cells in th eir sensitivity to macrophage cytotoxicity is determined by their MHC I expression. Separation of CD4 T cells from CD8 T cells deprives memo ry CD4 T cells of their resistance against macrophage cytotoxicity, su ggesting that memory T cells' resistance against destruction by macrop hages is controlled by regulatory T cells.