SPECIALIZED IMMUNOLOGICAL NICHES© 2006 Nature Publishing Group http://www.nature.com/natureimmunology

Voracious monocytes
Immature monocytes develop in the bone marrow, express
Gr-1hi and are unable to phagocytose antigens. In the Journalof Experimental Medicine, Randolph and colleagues challengethat view. Using fluorescent latex beads, they show that bonemarrow–resident Gr-1hi cells acquire antigen indirectly byphagocytosing neutrophils and B cells that acquire the beads
in the periphery and then migrate to the bone marrow. Afterleaving the bone marrow, Gr-1hi monocytes mature to become
macrophages and dendritic cells (DCs) and only then present
the retained antigens to lymphocytes. These data have
implications for how antigen is presented during infection withintracellular bacteria such as listeria, which are known to infectthe bone marrow niche.
DCBJ. Exp. Med. (22 February 2006) doi:10.1084/jem.20052119

RESEARCH HIGHLIGHTS

Niche-specific memory
Central (TCM) and effector (TEM) memory T cell subsets were identified during investigations of splenic, lymph node and blood T cells.
In the Journal of Immunology, Ahmed and colleagues compare gut
CD8+ memory T cells with recirculating TCM and TEM cells. Virusspecific gut CD8+ memory T cells differ in surface phenotype, contain more granzyme B, proliferate less and produce less interleukin
2, tumor necrosis factor and interferon-γ than their TCM and TEM
counterparts. These disparate characteristics of splenic and gut
memory CD8+ T cells are acquired gradually after virus infection
but are reversible and depend on persistent localization in the spleenor the gut. These data add a new dimension to the TCM-versus-TEM
paradigm and suggest that niche-specific factors might ensure thatmemory T cells are programmed to efficiently respond to nichespecific threats.
CBJ. Immunol. 176, 2079–2083 (2006)

Visualizing stem cells
Hematopoietic stem cells (HSCs) have not been visualized invivo because of difficulties of identifying true populations. In
the Proceedings of the National Academy of Science, Suzuki et al.
directly visualize HSCs in their bone marrow niche by generating ‘knock-in’ reporter mice in which green fluorescent protein (GFP) expression is driven by a tissue-restricted Gata2
promoter. Gata2-GFP expression correlates well with phenotypic and functional attributes of HSCs. In situ visualization ofGFP+ cells in trabecular bone shows discrete GFP+Sca1+ cells
in direct contact with osteoblasts near endosteal bone regions.
Time-lapse movies show that these cells are mostly immobile inthe bone marrow, in contrast to mobile GFP–Sca1– cells that can
be classified as early hematopoietic progenitor cells. These reporter
mice not only provide insights into where HSCs reside in thebone marrow but also will be a useful tool for further analysis of
HSC biology.
LAD
Proc. Natl. Acad. Sci. USA 103, 2202–2207 (2006)

Tolerizing movement
CCR7 is essential for the migration of CD4+ and CD8+ singlepositive thymocytes from the thymic cortex to the thymic medulla.
In Immunity, Takahama and colleagues demonstrate that cortexto-medulla migration is essential for the establishment of central
tolerance. CCR7-deficient thymocytes accumulate in the cortex,
from where they can exit the thymus in a sphingosine-1 phosphate
receptor–dependent way. Although thymic egress occurs in the absenceof CCR7, CCR7-deficient mice demonstrate autoimmune destructionof exocrine glands. Thymic epithelial cells expressing the autoimmune
regulator transcription factor (Aire), which is essential for thymocyte
exposure to peripheral tissue–restricted antigens, are localized exclusively in the medulla. After positive selection, single-positive thymocytes spend an additional 12 days in the thymus. These results suggestthat this ‘extended stay’ functions at least in part to impose central
tolerance by exposing newly generated single-positive thymocytes toperipheral tissue–restricted antigens.
CBImmunity 24, 165–177 (2006)

Research notes written by Christine Borowski, Douglas C. Braaten and Laurie
A. Dempsey.

NATURE IMMUNOLOGY VOLUME 7 NUMBER 4 APRIL 2006

NK cells in situ
In vitro studies have demonstrated functional crosstalk canoccur between natural killer (NK) cells and DCs, thereby
potentially influencing ensuing immune responses. Whether
such interactions occur in more physiological settings remains
unclear. In the Journal of Experimental Medicine, Germain andcolleagues use intravital and confocal imaging of mouse lymph
nodes to show that long-lived NK cell–DC interactions formin situ. NK cells are found in close proximity to paracorticaland medullary DC networks in uninflamed lymph nodes.
These NK cells are much less motile than T cells present in
the same lymph node. NK cells are rapidly recruited from thebloodstream into draining lymph nodes after infection with
Leishmania major. These newly immigrant NK cells localize
to the paracortical T cell areas of the lymph node, where theyalso form intimate contacts with DCs and express interferon-γ.
These imaging studies show that DC–NK cell communication
networks form in physiologically relevant scenarios and affectDC-mediated T cell activation.
LADJ. Exp. Med. (27 February 2006) doi:10.1084/jem.20051474

Immune privilege
Immune-privileged sites such as the central nervous system (CNS)
can be targets of infection and severe disease. In the Journal ofImmunology, Bergmann and colleagues characterize the mechanism
for maintaining CNS immune privilege after vaccination against
neurotropic coronavirus infection. Recrudescent coronavirus replication occurs because T cell–mediated immune control is lost.
Priming with virus antigen induces robust CD8+ T cell memory in
the CNS that effectively clears acutely replicating virus after challenge. Nevertheless, such effective T cell priming cannot prevent
viral recrudescence and loss of T cell–mediated control. Virus-specific CD8+ T cells become quiescent because antigen presentation
by CNS-resident cells is transient, as resident glial cells are found to
rapidly lose expression of both major histocompatibility complex
class I and class II molecules. Thus, although vaccination substantially enhances T cell immunity, intrinsic properties of immune
privilege sites can abrogate those effector functions.
DCB
J. Immunol. 176, 3062–3069 (2006)

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