T-cell activation

HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse. Gomez, T. S. et al. Immunity 24, 741–752 (2006)

Formation of the immunological synapse, which involves actin polymerization and recruitment of signalling molecules, is crucial for T-cell activation. Now, new research has implicated haematopoietic-lineage-cell-specific protein 1 (HS1) as a key regulatory adaptor protein in this process. Using T cells from Hs1−/− mice and T cells in which the expression of HS1 is suppressed, the authors showed that HS1 maintains F-actin at the immunological synapse and is required for the organization and maintenance of specific structures that are necessary for conjugate formation. Phosphorylation of HS1, by key signalling molecules in the synapse, is required for actin regulation and is important for the activation of interleukin-2 promoter. This protein is also important for maintaining VAV1, which regulates actin responses, at the synapse. So, HS1 is an actin-regulatory protein that is crucial for T-cell activation.

Evolution

Insect immunity shows specificity in protection upon secondary pathogen exposure. Sadd, B. M. & Schmid-Hempel, P. Curr. Biol. 16, 1206–1210 (2006)

Immunological memory and specificity characterizes adaptive immunity in vertebrates. Invertebrates can mount an immune response following pathogen exposure, but it was not clear whether this response could be specific. A new study now shows that insects can mount a specific immune response to a previously encountered pathogen. Sadd and Schmid-Hempel tested the immune system of Bombus terrestris (the bumblebee) to determine if it could show protection, specificity or both on exposure to bacterial pathogens following previous exposure. The authors found that the immune system of B. terrestris responded in a specific manner to previously encountered pathogens, even several weeks after the first exposure, and that this response was functionally protective. So, despite their broad differences, both vertebrate and invertebrate immune systems mount a specific protective response. The authors suggest that similar selective pressures on these different immune systems over evolutionary time might therefore have resulted in comparable solutions.

Apoptosis

Gimap4 accelerates T-cell death. Schnell, S. et al. Blood 108, 591–599 (2006)

By searching for genes that are differentially expressed during T-cell development, the authors of this study identified Gimap4 (GTPase, immunity-associated protein family member 4). Gimap4 expression was found to be induced initially during the early stages of T-cell development, turned off during positive selection and re-expressed thereafter, including by mature T cells. Despite this expression pattern, Gimap4−/− mice showed no defect in T-cell development. Instead, the authors found that, compared with wild-type cells, cultures of mature T cells from Gimap4−/− mice showed increased numbers of apoptotic cells versus dead cells following serum starvation or exposure to other apoptotic triggers. Further studies led the authors to conclude that GIMAP4 acts as an accelerator of the late stages of apoptosis and functions downstream of caspase-3 activation and phosphatidylserine exposure.