Volume 11 Issue 6, June 2010

Severe combined immunodeficiency conditions are devastating disorders of adaptive immunity. Although these diseases were initially treated by transplantation of allogeneic hematopoietic stem cells, the past 20 years has shown that these conditions are correctable by gene therapy.

Medullary thymic epithelial cells maintain tolerance by expressing peripheral self antigens. New data show that they also present these antigens, which leads to the deletion of conventional CD4⁺ T cells and the induction of regulatory T cells.

Chemoattractants direct the extravasation of leukocytes to the site of immune response. New data highlight the role of synaptotagmins and Rab proteins in leukocyte chemotaxis.

B cell–T cell interactions in germinal centers are needed to generate high-affinity antibodies. PD-1 signaling is now shown to influence the quality of germinal center responses.

Many pathogens induce a type I interferon response via a pathway dependent on the kinase TBK1 and transcription factor IRF3. However, LRRFIP1, a cytosolic sensor of DNA and RNA, triggers interferon production by a β-catenin-dependent signal.

Infection elicits cytokine production that can alter hematopoiesis. Potocnik and colleagues identify a unique IL-7Rα⁺c-Kit^hi progenitor subset that arises during acute malaria infection and gives rise to predominantly myeloid cells.

Intracellular nucleic acid sensors trigger the production of type I interferon. Cao and colleagues identify LRRFIP1 as a cytosolic nucleic acid–binding protein that mediates the production of type I interferon via a β-catenin-dependent pathway.

Synaptotagmins are calcium-dependent regulators of intracellular vesicle fusion. Luster and colleagues show that synaptotagmins SYT2, SYTL5 and SYT7 also regulate leukocyte chemotaxis by triggering uropod de-adhesion via the fusion of lysosomes with plasma membranes.

Thymic selection requires that thymocytes transit through distinct anatomical compartments. Weiss and colleagues report that the G protein regulator GIT2 integrates T cell antigen receptor and chemokine receptor signaling necessary for proper migratory activity and positive selection.

Medullary thymic epithelial cells are essential to the establishment of central tolerance by expressing peripheral tissue antigens. Klein and co-workers now show that these cells also mediate clonal deletion of CD4⁺ T cells.

Cytokine signaling is thought to be tightly localized in lymphoid tissues. Mohrs and co-workers show that interferon-γ and interleukin 4 signal to most lymphocytes throughout the reactive lymph node.

Interleukin 9 secretion contributes to allergic inflammation. Kaplan and colleagues identify the transcription factor PU.1 as being necessary for T_H9 differentiation and as a contributing factor in allergic airway inflammation.

PD-1 is commonly associated with inhibitory functions, yet it is highly expressed in follicular T cells. Shlomchik and colleagues find that PD-1 signaling in germinal centers is necessary for long-lived humoral immunity.