The role of B7 costimulation in CD4/CD8 T cell homeostasis

The effect of B7-mediated costimulation on T cell homeostasis was examined in studies of B7-1 (CD80) and B7-2 (CD86) transgenic as well as B7-defieien t mice. B7 overexpression in transgenic mice resulted in marked polyclonal peripheral T cell hyperplasia accompanied by skewing toward an increased pr oportion of CD8 single-positive cells and a decreased proportion of CD4 sin gle-positive cells in thymus and more markedly in peripheral T cells. B7-in duced T cell expansion was dependent on both CD28 and TCR expression. Trans genic overexpression of B7-1 or B7-2 resulted in down-regulation of cell su rface CD28 on thymocytes and peripheral T cells through a mechanism mediate d by intercellular interaction. Mice deficient in B7-1 and B7-2 exhibited c hanges that were the reciprocal of those observed in B7-overexpressing tran sgenics: a marked increase in the CD4/CD8 ratio in peripheral T cells and a n increase in cell surface CD28 in thymus and peripheral T cells, These rec iprocal effects of genetically engineered increase or decrease in B7 expres sion indicate that B7 costimulation plays a physiological role in the regul ation of CD4(+) and CD8(+) T cell homeostasis.