International Immunology 2008 20(7):NP; doi:10.1093/intimm/dxn067
© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
IN THIS ISSUE
 |
Matrix metalloproteinases and NK cell cytotoxicity
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|---|
Ligation of receptors such as NKG2D on NK cells to ligands on
tumour cells can trigger cytotoxicity. In this issue,
Mami-Chouaib and colleagues (p. 801) show that matrix metalloproteinases
(MMPs) can enable lung cancer cell lines to shed the ligands
and escape killing. Using MMP inhibitors, perhaps in combination
with IL-15, might circumvent this evasion mechanism.
|
Bam32 activates Erk in T cells
|
|---|
B lymphocyte adapter molecule of 32 kD (Bam32) is known to be
involved in BCR-mediated signalling. Here,
Samelson and colleagues (p. 811) used Bam32-deficient mice to show for the first time
that Bam32 is required for optimal TCR-induced Erk activation,
cytokine production, cell proliferation and cytoskeletal function
in CD4
+ T cells.
|
Levels of CD45 isoforms and T cell signalling
|
|---|
The expression of different CD45 isoforms is a well-known phenotypic
marker for lymphocyte subsets. The article by
Salmond et al. (p. 819) shows that the level of CD45 expression can be critical
for sensitivity to TCR stimulation, irrespective of the isoform.
The authors discuss implications for CD45-mediated positive
and a negative regulation of T cell signalling.
|
Activation of   cells by a probiotic
|
|---|
The probiotic strain
Escherichi coli Nissle 197 is known to
interact with T cells. The paper by
Sturm and colleagues (p. 829) shows that
E. coli Nissle, but not other probiotic bacteria
tested, has several effects on
cells. This might allow bridging
of the innate and adaptive responses against this bacterium.
|
The phenotype of alloreactive killer cells
|
|---|
Cytokine-induced killer cells (CIK), expanded
in vitro, show
in vivo graft-versus-tumour activity, but also graft-versus-host
responses.
Cignetti and colleagues (p. 841) depleted CD56
– cells from CIK populations derived from patients who had colorectal
cancer and had received haematopoietic cell transplants:
in vitro alloreactivity was minimal but antitumour activity was
retained.
|
Two pathways for Th1 generation by mycobacteria
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|---|
Different cell-wall components from mycobacteria can modify
immune responses to the bacteria, and mycobacterial extracts
are used for vaccines. The article by
Nakayama and colleagues (p. 849) shows that lipomannan and lipoaribinomannan from
Mycobacterium bovis potently enhance T
h1 responses and act either directly
on human CD4
+ T cells or indirectly via dendritic cells.
|
Regulatory T cells in SLE
|
|---|
The importance of regulatory T cells (Treg) in human systemic
lupus erythematosus is not yet established. Here,
Scheinecker and colleagues (p. 861) show that disease activity inversely
correlates with proportions of CD4
+CD25
hi Treg in the blood
and with their
in vitro suppressive capacity. The authors discuss
their results in the context of previous studies.
|
NKT cells break CTL tolerance to HBV
|
|---|
Hepatitis B virus (HBV) provokes only weak CTL responses, leading
to carrier status and/or progression to chronic hepatitis.
Ito et al. (p. 869) activated NKT cells, and thereby boosted CTL
responses in both wild-type and HBV-transgenic (carrier) mice.
IL-2 and CD40 ligand are crucial for the enhanced CTL induction.
|
Constitutive TLR-mediated B cell activation in lupus
|
|---|
Radioprotective 105 (RP105) is a Toll-like receptor (TLR) expressed
on B cells. The paper by
Miyake and colleagues (p. 881) shows
constitutive B cell activation by TLR2, TLR4 and RP105, especially
affecting IgG3 levels. The paper details how the lack of RP105
in lupus-prone mice led to amelioration of some, but not all,
steady-state disease features.
|
Oral antigens reduce numbers of T cells
|
|---|
The mechanisms operating in oral tolerance are incompletely
understood. In this issue,
Klugewitz and colleagues (p. 893) gave high-dose oral ovalbumin and showed reduced numbers of
transferred antigen-experienced memory CD4 cells or T
h1 cells,
especially in the liver. The authors discuss how the reduced
numbers occur; there was no evidence for induction of regulatory
cells or anergy.
|
Signalling pathways in keratinocyte antiviral responses
|
|---|
The epidermis is important in interactions between viruses and
innate immunity, and
Sayama and colleagues (p. 901) demonstrated
a wide range of cytokines and chemokines produced by keratinocytes
in response to double-stranded RNA. The authors then showed
that three major signalling pathways are each regulated by a
different set of cytokines/chemokines.
|
S1P1 agonism impairs dendritic cell migration
|
|---|
Immunosuppressants such as FTY720 and SEW2871 are agonists of
the widely expressed sphingosine-1-phosphate receptor, but have
different effects on the receptor. The article by
Mueller and colleagues (p. 911) details some of these differences and shows
that SEW2871 decreases human dendritic cell and murine Langerhans
cell migration. The authors also investigate effects on the
cytoskeleton and the signalling pathways involved.
|
ICAT is important for thymocyte development
|
|---|
ICAT (inhibitor of β-catenin and T cell factor 4) is a
natural inhibitor of a specific interaction in the Wnt pathway.
In mice in with ICAT overexpression,
Sen and colleagues (p. 925) show reduced numbers of thymocytes and mature T cells.
Thymocytes and activated T cells show increased apoptosis and
the authors define the role of Bcl proteins in this situation.
|
MHC-restricted suppression by CD8+CD122+ Tregs
|
|---|
Naturally occurring CD8
+CD122
+ regulatory T cells (Tregs) produce
IL-10 and suppress previously activated CD4
+ or CD8
+ T cells.
In this article,
Suzuki and colleagues (p. 937) show that naïve
CD8
+CD122
+ Tregs are initially activated via conventional, MHC-restricted
interactions involving the
βTCR, CD8 and target-cell MHC
class Ia.
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Matrix metalloproteinases and NK...
Bam32 activates Erk in...