Abstracts (complete list) - Wissenschaft Online

Benjamin Stoelcker, Kirsten Krätzel, Günther Eissner, Michael Pfeifer, Christian Schulz
NKG2D-triggered effector function of bronchial epithelial cell
activated alloreactive CD8+ T cells
Allogeneic hematopoietic stem cell transplantation (SCT) has emerged as a curative
therapeutic option still holding severe side effects including pulmonary toxicity. The
exact role of GvHD for the lung injury after SCT has still to be determined. Induction of
GvHD is considered to depend upon interactions between donor T cells and host APCs,
but it has recently been shown that non-haematopoetic allograft cells can directly
activate host CD8+ T cells. This prompted us to investigate in vitro the potential of
bronchial epithelial cells to activate allogeneic CD8+ T cells and to study the induced
cytotoxic effector functions.
The bronchial epithelial cell line BEAS-2B was shown to express MHC I, MIC A and B,
ULBP-2 and -3, ICAM1, CD70, B7-H1,-H2,-H3, but no or only very low levels of CD80
and CD86. Purified allogeneic CD3+ CD8+ CD4- CD16/56- T cells cocultured with
irradiated BEAS-2B in the presence of low dose IL-2 produced significant amounts of
IFNγ, upregulated alloantigen activation markers CD69 and HLA-DR and showed high
proliferation as compared to IL-2 alone stimulated T cells. Cytotoxicity assays
demonstrated that specific, Granzyme B-mediated cytolytic activity against BEAS-2B
was induced in the alloactivated CD8+ T cells. They showed increased expression of
NKG2D and their cytolytic activity was inhibited using a blocking anti-NKG2D antibody,
but not by blocking MHC I with antibody W6/32. IL-15, which has been shown to be
able to contribute to TCR-independent CTL effector function could not be detected in the
supernatants of the BEAS-2B/CD8+ T cell cocultures. This, together with the low dose
IL-2 used argues against the induction of LAK cells. Cold target inhibition assays with
K562 cells revealed that cytotoxicity was not the result of contaminating NK or NKT
cells.
Our in vitro data let us speculate that bronchial epithelial cell triggered NKG2Dsignalling
contributes to a MHC-unrestricted CTL effector function in lung-directed
alloreaction. This might be of clinical relevance for the course of GvHD after SCT.