Haematopoiesis

A stromal-cell derived membrane protein that supports haematopoietic stem cells. Ueno, H. et al. Nature Immunol. 31 March 2003 (doi:10.1038/ni916)

The bone-marrow microenvironment has a crucial supporting role in the growth, differentiation and survivial of haematopoietic stem cells (HSCs). Without bone-marrow stromal cells, HSCs cannot be maintained in vitro, even when cultured with a cocktail of growth factors. In this study, a retroviral-based signal-sequence trap method identified a new candidate HSC-supporting membrane protein, which the authors have named Kirre owing to its homology with the Drosophila myoblast attractant factor kirre. Kirre accumulated in the areas of contact between HSCs and stromal cells in culture, and abrogating expression of Kirre using small interfering RNA (siRNA) inhibited the capacity of bone-marrow stromal cells to support HSC proliferation in vitro. So, the authors propose that Kirre functions to maintain HSCs in an undifferentiated, proliferative state.

Cell Death And Immunity

Cell death induced by granzyme C. Johnson, H. et al. Blood 101, 3093–3101 (2003)

Although much is known about the functions of granzymes A and B, granzyme C has been less well studied. Here, Johnson et al. show that mouse granzyme C (which is closely related to human granzyme H) causes cell death with similar kinetics to granzyme B and is of equal potency. Cell death that is induced by granzyme C requires its protease activity, results in externalization of phosphatidylserine, nuclear condensation and single-stranded but not double-stranded DNA nicking. Granzyme C causes swelling and depolarization of mitochondria, and death induced by this granzyme does not involve caspase activation, cleavage of BID (BH3-interacting domain death agonist) or activation of the CAD nuclease.

T-Cell Signalling

SWAP-70-like adapter of T cells, an adapter protein that regulates early TCR-initiated signaling in TH2 lineage cells. Tanaka, Y. et al. Immunity 18, 403–414 (2003)

Here, Tanaka et al. describe the identification of SWAP70-like adaptor of T cells (SLAT), a protein that is selectively expressed at high levels by T helper 2 (TH2) cells but not TH1 cells. SLAT positively regulates IL-4 expression and negatively regulates IFN-γ expression. After antigen stimulation of the T-cell receptor (TCR) SLAT translocates to the immunological synapse, where it associates with the tyrosine kinase ZAP70. Transient overexpression of SLAT caused reduced association of ZAP70 with TCRζ and interfered with ZAP70, but not LCK, signalling. This study indicates a role for SLAT in the differentiation, activation and/or expansion of TH2 cells, but further studies are required to elucidate the mechanisms by which it acts.