News & Views in 2000

NKT cells can rapidly produce a diversity of immunoregulatory cytokines; does this make these cells aggressors or suppressors? New experiments now reveal their immunosuppressive function in tumor control and reiterate their pivotal position.

Although thyrocytes in two autoimmune diseases of the thyroid both express Fas and FasL, the conditions produce opposite results: either hyper- or hypothyroidism. This may be due to cytokine production indirectly supporting pro- or anti-apoptotic gene expression in thyrocytes.

“Lymphocyte subsets” brings to mind different types of T cells. New work indicates that B cells may also have distinct effector functions

The bite of the sandfly can both bring disease or provide protection. A report in a recent issue of Science indicates that infection with Leishmania can be severely impaired by previous bites from uninfected sandflies.

A recent paper in Nature sheds welcome light on the mechanism of somatic hypermutation by documenting the participation of double-strand DNA breaks.

Once natural killer cells identify their targets they engage their lysis machinery. Spontaneous, unlike antibody-dependent, cytotoxicity predominantly uses a Ras-independent pathway to accomplish this activation.

The innate immune system relies heavily upon Fc receptors to rid the body of pathogens. An Fc receptor that recognizes IgM has finally been cloned.

Lymphocyte memory—is there a requirement for the continual presence of antigen or not? In a recent issue of Nature an elegant series of genetic manipulations from Maruyama et al. makes a strong case for the persistence of B cell memory in the absence of antigen.

In a new twist, the cytokine IL-10, if present when leukocytes are activated, can disconnect chemokine receptors from signaling for cell migration. The receptors act as a “sink” for soaking up chemokines, thus providing the perfect decoy.

B cell maturation is affected by factors found in the microenvironment of the bone marrow. A new tachykinin neuropeptide family member, HK-1, and TSLP both seem to aid the pre-B cell stage.

The NF-κB family of transcription factors are central to signaling from Toll family receptors. The IKKγ protein of Drosophila has been found to regulate NF-κB family–member Relish, but not the similar protein DIF, in the fly innate immune response.

Ever since it was proposed that distinct subsets of dendritic cells induce distinct subsets of T cells, immunologists have been struggling to reconcile those conclusions with other data. New experiments now illuminate a different interpretation.

How do T cells recognize allogeneic MHC molecules with such ferocity? The first crystal structure of an allo-MHC complexed with peptide and T cell receptor begins to reveal the answer.

Antigen receptor editing is no longer the province of B cells alone. T cells also can be caught in the act, given the right system. The T cell receptors of double positive thymocytes that recognize self antigens on the cortical epithelium with dangerously high affinity will undergo editing until they get it right.

Activation of Ras is key for lymphocyte development and function. The understanding of Ras activation in T cells now takes an important step forward by the initial analysis of mice lacking the Ras activator RasGRP.

It is becoming more apparent that some B cells do not carry the same antigen receptors throughout their life. B cells that have edited their receptors have now been found in humans as rare cells that accumulate in arthritic joints.

The complement inflammatory cascade is crucial to our innate ability to ward off infection. Two papers now provide evidence linking C5 and C3a to murine airway hyperresponsiveness, a partial model of human asthma. Surprisingly, these complement proteins appear to have opposite effects.

T cell activation usually requires TCR engagement by antigen and another, costimulatory, signal. Modeling studies now indicate that this second signal may only slightly enhance TCR signaling, but nevertheless results in an exponential increase in cell numbers.

The proto-oncogene BCL6 participates in the regulation of immune responses; a lack of it leads to generalized type 2 inflammation. Macrophage chemokine genes have now been identified as targets for BCL-6 repression and perhaps induce this inflammation.

How do T cells that are specific for pancreatic islet cell antigens cause diabetes? A recent paper in Nature provides evidence from NOD mice that the killer T cells responsible increase their avidity as the disease progresses—removing the high avidity clones prevents disease.