Abstracts (complete list) - Wissenschaft Online

J. Kolja Hegel, Pushpa Pandiyan, Paula Kolar, Karin Knieke, Steven L. Reiner, Monika
Brunner-Weinzierl
CD152 (CTLA-4) utilizes Eomesodermin, but not T-bet, for
regulating effector function of individual CD8 T lymphocytes:
Implication for tumor therapy
Immune responses of CD8 T lymphocytes are primarily regulated by positive and
negative costimulatory molecules such as CD28 and CD152 (CTLA-4), respectively. We
were able to show that surface expression of CD152 is highly up regulated on activated
CD8 T lymphocytes already during primary immune responses, suggesting a prominent
regulatory role. Traditionally, CD152 blockade or deficiency was thought to only
increase CD4 T cell help or enhance the overall frequency of cytotoxic CD8 T cells
responding an antigenic stimulus. We could now reveal that CD152 enhances effector
functions (cytotoxicity and cytokine response) of individual CD8 T cells. Mechanistically,
we could demonstrate that signals induced by CD152 reduce the frequency of IFNgamma
and GranzymeB expressing CD8 T cells independently of T-bet by selectively
inhibiting Eomesodermin downstream of the ERK/MAPK pathway. Enhanced cytotoxicity
of individual CD8 cells primed in the absence of CD152 signaling could be demonstrated
in vivo. These novel insights could explain the efficacy of anti CD152 treatment for
tumor rejection.