T-Cell Signalling

Induction of T helper type 2 immunity by a point mutation in the LAT adaptor.Aguado, E. et al. Science 296, 2036–2040 (2002)

A LAT mutation that inhibits T-cell development yet induces lymphoproliferation.Sommers, C. L. et al. Science 296, 2040–2043 (2002)

The adaptor protein LAT (linker for activation of T cells) links the T-cell receptor (TCR) to downstream signalling effectors. Two groups have now generated mice that are homozygous for a mutation of a single LAT tyrosine residue (Tyr136) to investigate the role of this residue in vivo. Both groups report an early block in T-cell differentiation and the accumulation of polyclonal CD4+ helper T cells in the periphery. Aguado et al. show that these T cells produce large quantities of type-2 cytokines, which results in tissue eosinophilia and the secretion of IgE and IgG1 by plasma cells. Sommers et al. analysed TCR signalling and showed that the activation of PLC-γ and NFAT, calcium signalling, IL-2 production and cell death are defective in these mice. These studies highlight the crucial role of LAT in T-cell development and homeostasis.

Transplantation

Allogeneic β-islet cells correct diabetes and resist immune rejection.Pericin, M. et al. Proc. Natl Acad. Sci. 99, 8203–8206 (2002)

Usually, allogeneic MHC-incompatible cell grafts are rejected rapidly by immunocompetent hosts. Here, Pericin et al. successfully correct streptozotocin-induced diabetes by transplanting fully MHC-mismatched insulin-producing β-islet cells under the kidney capsule of recipient mice. This was made possible by the generation of a growth-regulated, transformed endocrine cell line that could be transplanted into recipients without contaminating passenger leukocytes. The grafts that controlled hyperglycaemia were not rejected for >100 days.

T-Cell Responses

Programmed contraction of CD8+ T cells after infection.Badovinac, V. P., Porter, B. B. & Harty, J. T. Nature Immunol. 3, 619–626 (2002)

Normally, the contraction phase of a T-cell response is correlated with clearance of the pathogen, but are these events mechanistically linked? This study indicates that for CD8+ T cells, the contraction phase is actually pre-programmed and, unlike the expansion phase, it is not dependent on the continued presence of available antigen. The kinetics of the contraction phases of CD8+ T-cell responses to viral or bacterial infection in mice were shown to be independent of the quantity of available antigen, duration of infection or magnitude of T-cell clonal expansion. These results indicate that the contraction of CD8+ T-cell populations is programmed to occur even if a pathogen has not been cleared successfully.