B7-h1 expressed by activated CD8 T cells is essential for their survival

V Pulko, KJ Harris, X Liu, RM Gibbons… - The Journal of …, 2011 - journals.aai.org
V Pulko, KJ Harris, X Liu, RM Gibbons, SM Harrington, CJ Krco, ED Kwon, H Dong
The Journal of Immunology, 2011journals.aai.org
An immunoinhibitory role of B7 homologue 1 (B7-H1) expressed by non-T cells has been
established; however, the function of B7-H1 expressed by T cells is not clear. Peak
expression of B7-H1 on Ag-primed CD8 T cells was observed during the contraction phase
of an immune response. Unexpectedly, B7-H1 blockade at this stage reduced the numbers
of effector CD8 T cells, suggesting B7-H1 blocking Ab may disturb an unknown function of
B7-H1 expressed by CD8 T cells. To exclusively examine the role of B7-H1 expressed by T …
Abstract
An immunoinhibitory role of B7 homologue 1 (B7-H1) expressed by non-T cells has been established; however, the function of B7-H1 expressed by T cells is not clear. Peak expression of B7-H1 on Ag-primed CD8 T cells was observed during the contraction phase of an immune response. Unexpectedly, B7-H1 blockade at this stage reduced the numbers of effector CD8 T cells, suggesting B7-H1 blocking Ab may disturb an unknown function of B7-H1 expressed by CD8 T cells. To exclusively examine the role of B7-H1 expressed by T cells, we introduced B7-H1 deficiency into TCR transgenic (OT-1) mice. Naive B7-H1–deficient CD8 T cells proliferated normally following Ag stimulation; however, once activated, they underwent more robust contraction in vivo and more apoptosis in vitro. In addition, B7-H1–deficient CD8 T cells were more sensitive to Ca-dependent and Fas ligand-dependent killing by cytotoxic T lymphocytes. Activation-induced Bcl-x L expression was lower in activated B7-H1–deficient CD8 T cells, whereas Bcl-2 and Bim expression were comparable to the wild type. Transfer of effector B7-H1–deficient CD8 T cells failed to suppress tumor growth in vivo. Thus, upregulation of B7-H1 on primed T cells helps effector T cells survive the contraction phase and consequently generate optimal protective immunity.
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