International Immunology 2008 20(9):NP; doi:10.1093/intimm/dxn096
© 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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T helper cells and T suppressor cells cooperate to regulate responsiveness: a critical essay
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In this review,
Melvin Cohn (p. 1107) puts regulatory T cells
into their biological context. Thus the regulatory T cell family
must consist of T helper cells and T suppressor cells: the former
provide effective responses; the latter control the magnitude
of response, minimising pathology. The author argues that T
suppressor cells have no role in self/non-self discrimination.
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LFA-1 and TCR thresholds in vivo
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Leukocyte function-associated antigen 1 (LFA-1) affects TCR
thresholds
in vitro.
Shibuya and colleagues (p. 1119) examined
in vivo effects in LFA-1-deficient mice, which respond better
to high-dose ovalbumin and are more susceptible to high-dose
collagen-induced arthritis. LFA-1 and TCR cooperation in sustaining
Erk1/2 phosphorylation is also dose dependent. These results
show clear physiological effects of LFA-1 on TCR thresholds.
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Production and function of IL-17 in salmonellosis
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The role of T
h17 cells in intracellular bacteria infection remains
unclear, especially at late stages. In this study,
Alber and colleagues (p. 1129) show that IL-17A–/– mice survive
infection with
Salmonella Enteritidis but have a larger bacterial
burden. Neutrophil and DTH reactions are reduced. IL-17A is
produced by
T cells and other CD4
– cells, as well as
CD4
+ cells.
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IL-1 isoforms and S. pneumoniae infection
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Pneumococcal bacteria are a major cause of human disease, and
cytokines are important for host defence. Using genetically
deficient mice,
Mizrachi-Nebenzahl and colleagues (p. 1139) evaluated the roles of IL-1
, IL-1β and IL-1 receptor antagonist
in protection against
Streptococcus pneumoniae. IL-1β appears
to play a relatively major role, in part via neutrophil recruitment
and activation.
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A unique regulatory T cell population in decidua
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While investigating how foetuses are not rejected by the mother,
Amsalem et al. (p. 1147) show that human decidual lymphocytes
inhibit
in vitro activation of blood mononuclear cells. The
cells responsible are phenotypically natural regulatory T cells
(Tregs) but have non-conventional properties; the authors propose
that these comprise a functionally unique regulatory lymphocyte
subset.
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NK cells recognise BCG via TLR2
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In this article,
Moretta and colleagues (p. 1155) show that,
in direct response to
Mycobacterium tuberculosis bacillus Calmette–Guérin
(BCG), NK cells gain an activated phenotype, release cytokines
and kill target cells more efficiently. Toll-like receptor 2
seems to be important for these effects, and the authors discuss
how cross-talk between dendritic cells and NK cells might help
to combat mycobacterial infection.
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RSV blocks TLR signalling and IFN production
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Seya and colleagues (p. 1169) show that respiratory syncytial
virus (RSV) induces little IFN-β in monocyte-derived dendritic
cells early in infection. RSV binding inhibits Toll-like receptor
3 (TLR3) signalling and IFN production and this effect is mediated
by the envelope G glycoprotein. As detailed here, TLR4 signalling
and fusion-glycoprotein-mediated IFN production are also inhibited.
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Adam10 activates Notch in T cell development
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In mice with thymocyte-specific disruption of the gene for Adam10
(a disintegrin and metalloprotease 10),
Wu and colleagues (p. 1181) find impaired activation of Notch1 and its downstream
targets. The T cell development defect is similar to that caused
by Notch1 knockout, indicating that Adam10 is critical for proteolytic
activation of Notch1 in developing T cells.
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Human Th1 and Th2 cell phenotypes
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Using eight-colour flow cytometry of surface markers and cytokine
production by human CD4
+ cells,
Takiguchi and colleagues (p. 1189) identify several useful phenotypes. For example, there
are three subsets among CD27
+CD28
+ cells: naïve; central
memory; and T
h0 or T
h1 effector memory cells. Among CD27
–CCR7
–CD45RA
– cells, CD28
– cells are predominantly T
h1, whereas CD28
+ cells contained T
h1 and T
h2 cells.
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Role of IL-13 in basophil responses
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The effects of IL-13 on basophil responses to parasitic infection
are still not established. In this article,
Min and colleagues (p. 1201) describe and discuss a novel observation: T-cell-derived
IL-13 in mice infected with
Nippostrongylus brasiliensis promotes
basophil production; however, this IL-13 appears not to affect
basophil survival
in vivo.
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Immortalised bone marrow stem cells
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Murine stem cells have limited capacity to expand in culture,
hampering efforts to manipulate them and generate differentiated
cells more efficiently. Overexpression of the transcription
factor HOXB4 or nucleoporin 98 (NUP98) increases stem cell expansion.
Here,
Karjalainen et al. (p. 1211) demonstrate almost limitless
expansion of apparently normal stem cells if the cells transgenically
express a NUP98–HOXB4 fusion protein.
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Suppression of dendritic cell maturation by fibroblasts
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Dendritic cell (DC) maturation is normally suppressed in a stromal
microenvironment.
Yoshimura and colleagues (p. 1219) co-cultured
bone-marrow-derived DCs and mouse embryonic fibroblasts
in vitro.
Contact-dependent suppression affects DC class II, CD40 and
CD86 expression (important for interaction with T cells), whereas
fibroblast-derived prostaglandin E
2 affects DC inflammatory
cytokine production in a contact-independent manner. Potential
mechanisms are detailed.
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IFN-, cyclophosphamide and type 1 diabetes
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Cyclophosphamide accelerates diabetes in the non-obese diabetic
(NOD) strain.
Kanagawa and colleagues (p. 1231) used NOD mice
with disrupted IFN-
signalling; here, cyclophosphamide not only
confers permanent protection against the development of diabetes,
but also reverses the pathogenic features of ongoing diabetes.
Regulatory T cells appear to mediate these effects, and the
authors discuss the implications.
CiteULike 
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