International Immunology 2008 20(11):NP; doi:10.1093/intimm/dxn121
© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
IN THIS ISSUE
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Human Th17 cells
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T
h17 cells continue to be intensively studied, and several controversies
remain. In this review,
Romagnani and colleagues (p. 1361) compare
and contrast the involvement of various cytokines in the generation
of T
h17 cells in mice and humans. They also describe the phenotype
of human T
h17 cell precursors, and the role of T
h17 cells in
immunopathology.
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IVIg induces signals in IgG+ B cells
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Intravenous immunoglobulin (IVIg) is used for many inflammatory
and autoimmune disorders.
Néron and colleagues (p. 1369) show increased phosphorylation of kinases ERK1/2 and Akt, and
of the adapter Gab1, in IgG
+ human B cell lines exposed to IVIg.
Similar effects occurred in human blood B cells, specifically
in IgG
+ cells. The authors discuss implications for the mechanisms
of action of IVIg.
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CSR featuring AID-independent DNA breaks
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During B cell class-switch recombination (CSR), uracil-DNA glycosylase
(UNG) excises uracils generated, for example, by activation-induced
deaminase (AID). Here,
Max and colleagues (p. 1381) report that
most single-strand breaks in the antisense strand of switch
regions are UNG-dependent but not AID-dependent early in CSR.
They speculate that, as well as AID, another cytosine deaminase
can operate in CSR.
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Trophoblast cells trigger cytokines from decidual NK cells
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In this article,
Moretta and colleagues (p. 1395) show that
whereas activated human blood NK cells lyse trophoblast cell
lines, decidual NK cells (dNK cells) do not — instead
secreting a ‘non-classical’ set of cytokines, particularly
IL-8. As well as the implications for tolerance to foetal antigens,
the authors discuss how cytokines from dNK cells may affect
angiogenesis and placental development.
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Differential effects of PRAT4A on TLR functions
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Protein associated with TLR4 A (PRAT4A) is a chaperone affecting
the function and trafficking of many Toll-like receptors (TLRs).
Miyake and colleagues (p. 1407) describe variations in the strength
and location of associations between PRAT4A and TLR2, TLR4,
or TLR9; likewise, a mutant PRAT4A differentially affects trafficking
of TLRs. The findings will help us to understand how responses
to pathogens are coordinated.
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PKC directs IRF-4 expression and  gene rearrangement
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Here,
Kitamura and colleagues (p. 1417) show that anti-µ
cross-linking is similar to BLNK (B-cell linker) reconstitution
in affecting the pre-BCR; thus, BLNK can cross-link and downregulate
the pre-BCR. Protein kinase C
(PKC
) is a crucial molecular link,
downstream of the pre-BCR and BLNK, for IRF-4 (interferon regulatory
factor 4) induction and thereby promotes
-gene rearrangement
during pre-B-cell differentiation.
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Disruption of sphingomyelin impairs TCR signalling
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Although sphingomyelin is a major component of lipid rafts,
direct evidence of its importance for TCR signalling is lacking.
Using T cells with knocked-down sphingomyelin expression,
Umehara and colleagues (p. 1427) show severe impairment of many features
that are typical of T cell activation. The authors conclude
that sphingomyelin is indeed crucial for efficient T cell signal
transduction.
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Using a peptide analogue of OSP to treat EAE
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Among myelin components, oligodendrocyte-specific protein (OSP)
is relatively poorly studied as an autoantigen. In this article,
Ben-Nun and colleagues (p. 1439) delineate the major encephalitogenic
T-cell epitope in SJL/J mice; a peptide analogue suppresses
development of experimental autoimmune encephalomyelitis (EAE)
and reverses symptoms of ongoing EAE. There are clear implications
for the pathogenesis and potential treatment of multiple sclerosis.
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A CTL epitope from P. falciparum merozoites
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Initially using a predictive algorithm,
Pascolo and colleagues (p. 1451) identify the first CTL epitope from the merozoite
stage of
Plasmodium falciparum. Mass-spectrometry confirmed
that the epitope is processed naturally and it acts as a target
for cytotoxic HLA-A2-restricted CTLs. The authors speculate
that the epitope might be used to monitor anti-malaria responses
and also in vaccination strategies.
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CIITA promoter hypermethylation inhibits class II upregulation
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Using a variant of the myelomonocytic cell line THP-1 that does
not upregulate MHC class II after treatment with IFN-
,
De Lerma Barbaro and colleagues (p. 1457) show that the defect is due
to hypermethylation of CIITA promoter IV. The authors discuss
the implications of this epigenetic mechanism for tumour evasion
of immune responses.
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Local inflammation cures tumours and triggers memory
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Here,
Nelson and colleagues (p. 1467) use a mouse model of malignant
mesothelioma to show that direct injection of IL-2 and anti-CD40
into large tumours eradicates both that tumour and distant ones.
Tumour eradication requires collaboration between CD8
+ T cells
and neutrophils, and long-term memory responses are triggered.
The authors discuss using solid tumours as an
in situ ‘vaccine
site’.
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Human Th17 cells
IVIg induces signals in...