Volume 10 Issue 9, September 2009

The authors recount their discovery of how pathogen-induced interleukin 12 production leads to T_H1 T cell polarization. Simultaneously they discovered the suppressive cytokine interleukin 10 inhibits antigen-presenting cells, thus regulating development of T_H1 cells.

Macrophages infected with human immunodeficiency virus type 1 emit long intercellular conduits that shuttle the viral protein Nef to bystander B cells, where it impairs cellular function and immunoglobulin class switching.

While promiscuous expression of tissue-specific antigens (TSAs) in the thymus is essential for self-tolerance, immunologically relevant TSA expression may also occur in the secondary lymphoid organs. A new study links the transcriptional regulator Deaf1 with altered TSA expression in the secondary lymphoid organs and autoimmune diabetes.

Like every metazoan species hosting a gut flora, drosophila tolerate commensal microbiota yet remain able to mount an efficient immune response to food-borne pathogens. New findings explain how the quantity of reactive oxygen species in the gut is 'tuned' to microbial burden and how intestinal immune homeostasis is thereby maintained.

Foxp3 expression is not stable and may be extinguished both in vitro and in vivo in regulatory T cells that convert into proinflammatory effector T cells. The loss of Foxp3 in regulatory T cells under autoimmune conditions may result in the conversion of suppressor T cells into highly autoaggressive lymphocytes.

The gut immune system distinguishes commensal from dangerous microbes. Lee and colleagues delineate a pathway that 'fine tunes' the production of microbicidal reactive oxygen species to combat infections efficiently while tolerating commensal microbes.

The mediators that drive the progressive phase of multiple sclerosis remain undefined. Weiner and colleagues find that 15α-hydroxycholestene is expressed abundantly only during progressive multiple sclerosis and activates macrophages, microglia and astrocytes via poly(ADP-ribose) polymerase 1.

In vitro studies suggest that the adaptor TANK is needed for the production of type 1 interferon. Using TANK-deficient mice, Akira and colleagues instead find that TANK negatively regulates Toll-like receptor and B cell antigen receptor signaling in vivo.

SAP family adaptors, including SAP, EAT-2 and ERT, individually influence natural killer cell function. Veillette and colleagues show that natural killer cells lacking all three adaptors fail to eliminate unwanted hematopoietic cells.

In response to some signals, dendritic cells can become tolerogenic. Rabinovich and colleagues show that galectin-1 drives the differentiation of tolerogenic DCs via a circuit involving interleukins 27 and 10.

The polarization of naive CD4⁺ T cells to become T helper type 2 cells requires the transcription factor GATA-3. Sen and colleagues show that T cell antigen receptor signals induce interleukin 4–independent but TCF-1–β-catenin–dependent early expression of GATA-3.

The stability of expression of the transcription factor Foxp3 in vivo has not been thoroughly assessed. Bluestone and colleagues find that Foxp3 expression can be unstable and that cells that lose Foxp3 expression can assume a proinflammatory autoaggressive phenotype.

Patients infected with human immunodeficiency virus (HIV) have profoundly dysfunctional T and B cell populations. Cerutti and colleagues show that HIV-infected macrophages form long-range conduits that deliver the immunosuppressive HIV protein Nef to distal B cells, inhibiting their function.

B cell antigen receptors containing immunoglobulin G (IgG) or IgE, but not those containing IgM, show enhanced signaling. Wienands and colleagues trace this boosted signaling capacity to conserved IgG and IgE cytoplasmic tyrosine residues that recruit the adaptor Grb2.

Expression of peripheral tissue antigens may be important for peripheral T cell tolerance. Fathman and colleagues demonstrate involvement of the transcription factor Deaf1 in maintaining this expression and link a Deaf1 isoform with type 1 diabetes.