Abstracts (complete list) - Wissenschaft Online

Zulema Cabail, Holger Hoff, Heike Hirseland, Steven Nadler, Gerd R. Burmester, Monika
C. Brunner-Weinzierl
Longevity of CD28null T Lymphocytes is abrogated by CTLA-
4Ig treatment
CTLA4Ig engages CD80 and CD86 on antigen-presenting cells, which are both ligands
for CD28 and CD152 on T cells. CTLA4Ig-treatment has demonstrated efficacy in
treating rheumatoid arthritis and psoriasis. The traditional view of the mechanism of the
CTLA-4Ig treatment is inhibition of CD28-costimulation preventing activation of
inflammatory T lymphocytes.
In autoimmune diseases such as rheumatoid arthritis, CD28null T cells accumulate in
the joint which show high IFN• production and longevity. In this study, we used
CTLA4Ig (abatacept•) to investigate the CD80/CD86 costimulatory requirements of
heterogeneous CD28null T cells. First we could show that despite the loss of CD28
expression these cells are able to express intracellular CD152. Using a sensitive staining
method, we demonstrate that they also express CD152 at their cell surface. In vitro
activation of CD28null CD4 or CD8 T cells in the presence of CTLA4Ig leads to enhanced
frequencies of AnnexinV+ T Lymphocytes: 10% for CD8 and 25% for CD4 T
lymphocytes. IDO activation by CTLA-4Ig engagement of CD80 and CD86 was excluded.
Their Fas -expression at the cell surface was upregulated independently of CTLA-4Ig
treatment. Apoptosis induction was confirmed demonstrating enhanced Caspase
activation in CD28null cells stimulated under CTLA-4Ig treatment. These results suggest
that the efficacy of the CTLA4Ig treatment might be, at least in part, due to absent
CD152 signalling in inflammatory lymphocytes inducing their elimination by apoptosis.