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Departments of Microbiology/Immunology and Medicine and The Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202;
The Walther Cancer Institute, Indianapolis, IN 46208; Departments of
Molecular Virology and Host Defense, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426; and Departments of
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Molecular Immunology,
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Gene Expression Sciences, and
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Protein Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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, a known B cell chemoattractant.
CKß-11/MIP-3ß/ELC induced actin polymerization in lymphocytes, and
chemotaxis was completely blocked by pertussis toxin showing its
receptor, most likely EBI1/BLR2/CCR7, is coupled to a Gi
protein. CKß-11/MIP-3ß/ELC induced calcium mobilization in
lymphocytes, which could be desensitized by SDF-1, suggesting possible
cross-regulation in their signaling. Human CKß-11/MIP-3ß/ELC
attracted murine splenocytes suggesting functional conservation of
CKß-11/MIP-3ß/ELC between human and mouse. The efficacy of
chemoattraction by CKß-11/MIP-3ß/ELC and tissue expression of its
mRNA suggest that CKß-11/MIP-3ß/ELC may be important in trafficking
of T cells in thymus, and T cell and B cell migration to secondary
lymphoid organs. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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10
kDa, activating, suppressing, and attracting cells with relatively
specific activities. Most chemokines belong to either the CC or CXC
family, depending on the spacing between the first two cysteine
residues (1, 2, 3, 4). Two recently cloned chemoattractants, lymphotactin and
fractalkine, do not fit into this conventional grouping. Lymphotactin
is missing the first and third cysteine residues (5), and fractalkine
is membrane bound and has a CX3C motif (6, 7). In humans,
the CC chemokine genes are found on chromosome 17, while genes of CXC
chemokines are clustered on chromosome 4. However, genes for the human
fractalkine (6) and thymus- and activation-regulated chemokine (8) are
found on chromosome 16, and genes for the human lymphotactin (5) and
liver- and activation-regulated chemokine (9) are found on chromosomes
1 and 2, respectively. The primary function of chemokines appears to be
the chemoattraction of various cells, especially leukocytes, in a
haptotactic gradient-dependent fashion. Depending on the type of target
cells and place of action, chemokines can be involved in diverse
biologic processes such as inflammation, angiogenesis, regulation of
cell proliferation and maturation, and leukocyte homing or migration.
Some chemokines, such as IL-8, MIP-1ß3
and RANTES, are reported to modulate integrin adhesion and thought to
be important in migration of cells from one environment to another
(10, 11, 12, 13). SDF-1, a CXC chemokine, has been reported to attract
lymphocytes, monocytes, and hemopoietic progenitor cells (14, 15, 16, 47)
and, thus far, appears to be one of the most efficacious
chemoattractants for T cells among known CC and CXC chemokines. CKß-11 was identified as an expressed sequence tag (EST) from a human fetal spleen library by Human Genome Sciences (Rockville, MD). This chemokine was expressed in mammalian cells and the resulting protein was characterized using various leukocyte cell populations. MIP-3ß (17) and EBI1-ligand chemokine (ELC) (18) were recently reported to be identical to CKß-11 and the ligand for BLR2/EBI1/CCR7 (18). The gene for human CKß-11/MIP-3ß/ELC was found on chromosome 9 and its mRNA was detected in thymus, lymph nodes, lung, and intestine (18). We report here that CKß-11/MIP-3ß/ELC is a strong chemoattractant for T cells expressing CD4, CD8, CD45RO, and CD45RA, and for mature B cells, but not for monocytes and granulocytes. It also stimulates actin polymerization in lymphocytes and its signaling for chemotaxis is abolished by pertussis toxin. Calcium mobilization by CKß-11/MIP-3ß/ELC in lymphocytes is desensitized by another efficacious chemoattractant, SDF-1, suggesting a possibility of cross-regulation of signaling between the two efficacious lymphocyte chemoattractants.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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CKß-11/MIP-3ß/ELC was initially identified at Human Genome Sciences by random sequencing of expressed sequence tags in a cDNA library from human fetal spleen. A full length clone was subsequently identified and sequenced. CKß-11/MIP-3ß/ELC was expressed in Chinese hamster ovary (CHO) cells. For subcloning into an expression vector, the CKß-11/MIP-3ß/ELC coding region was amplified by PCR using the cDNA clone as substrate and the following pair of 5'-TC CCC GCG GCC ACC ATG GCC CTG CTA CTG GCC-3' (SacII site underlined and initiator methionine codon in bold) and 5'-GC TCT AGA CTA TCA GCG CCC TGG GCC ACG CTG GAT ACG GAT ACT TTT GCT CAA TGC TTG ACT CGG ACT-3' (XbaI site underlined) oligonucleotide primers. The PCR product was digested with ScaII and XbaI, subcloned into an intermediate vector, and sequenced, and then recloned into mammalian cell expression vector pCDN (19). The resulting plasmid was linearized with PvuI and introduced into a CHO cell line derivative by electroporation, and a polyclonal population of transformed cells with amplified vector copy number was selected by growth medium lacking nucleotides and containing methotrexate (20). Medium from the CHO stable cell line was used for purification of CKß-11/MIP-3ß/ELC.
Purification and analytical characterization of CKß-11/MIP-3ß/ELC from CHO-conditioned media
Purification, N-terminal analysis, and matrix-assisted laser desorption ionized (MALDI) mass spectrometry for CKß-11/MIP-3ß/ELC was conducted as described by Berkhout et al. (21) except that CKß-11/MIP-3ß/ELC-conditioned medium was substituted for MCP-4-conditioned medium. N-terminal sequence analysis of the CHO-derived purified CKß-11/MIP-3ß/ELC showed the N-terminal sequence of the mature secreted protein to begin at glycine-22. MALDI-mass spectrometry showed the major peak (8182 Da) to be lower in mass than the expected 8800 Daltons, suggesting that proteolytic cleavage had resulted in loss of five amino acids from the C terminus of the expected 77-amino acid protein.
Abs and chemokines
mAbs, conjugated with fluorescent dyes, FITC, phycoerythrin
(PE), or tri-color, to human CD3 (clone S4.1), CD8 (clone 3B5), CD45RA
(clone MEM56), CD45RO (clone UCHL1), and CD19 (clone SJ25-C1) were
obtained from Caltag (Burlingame, CA). PE-conjugated mAb to human CD4
(clone SK3) was obtained from Becton Dickinson (San Jose, CA). SDF-1
was a kind gift from Dr. Ian Clark-Lewis (University of British
Columbia, Vancouver, Canada). MIP-1, MIP-1ß, RANTES, monocyte
chemoattractant protein (MCP)-1, and IL-8 were purchased from R&D
Systems (Minneapolis, MN).
Cell isolation
Peripheral blood buffycoat was obtained from the Central Indiana Regional Blood Center (Indianapolis, IN), diluted 1:3, layered on Ficoll-Paque (1.077 g/ml) (Biochem KG, Berlin, Germany), and centrifuged for separation of low density mononuclear cells from RBC and polymorphonuclear cells. Bone marrow aspirates were obtained from healthy donors after receiving informed consent. Aspirates were diluted 1:2 with PBS (pH 7.4) and layered on Ficoll-Paque for centrifugation. Mononuclear cells were collected from the interphase of Ficoll-Paque and serum layers and washed twice with PBS (pH 7.4).
For lymphocytes, mononuclear cells were incubated overnight in plastic culture flasks to remove adherent monocytes. For total leukocytes containing granulocytes, 1 ml of peripheral blood buffycoat was added to 9 ml of hypotonic NH4Cl buffer and incubated at room temperature for 5 min to lyse RBCs. The cells were washed twice with PBS (pH 7.4).
In vitro two-chamber migration assay for leukocytes
Chemokine-dependent chemotaxis was assayed on various leukocytes by an in vitro two-chamber migration assay followed by flow cytometry (15, 22). One hundred microliters of cells in RPMI 1640 medium supplemented with 0.5% BSA was added to the upper chamber of Costar Transwells (6.5 mm diameter, 5-µm pore size, polycarbonate membrane), and chemokines were added to the upper and/or lower chamber to form various chemokine gradients. A total of 5 x 105 mononuclear cells were added to the upper chamber of the Transwell and incubated 2 h for monocyte migration and 3 h for lymphocyte migration. After collecting cells in suspension, 0.5 ml of 5 mM EDTA was added to the lower chamber for 15 min at 37°C to detach adherent cells such as monocytes and granulocytes from the bottom of wells. Detached cells were combined with the previously collected suspension cells for cell counting. Migrated monocytes and lymphocytes were counted by FACscan (Becton Dickinson) for 20 s by gating on appropriate populations of cells using forward-scatter and side-scatter channels. For counting CD3+ T cells and CD19+ B cells, migrated lymphocytes were stained with mAbs to CD3 and CD19, respectively conjugated with FITC and PE (Caltag), and CD3+CD19- T cells and CD3-CD19+ B cells were counted by FACscan for 20 s. The amount of all mAbs used to stain migrated cells in each well was 500 ng in 50 µl staining buffer (1% BSA and 0.01% NaN3 in PBS, pH 7.4). For CD45RA+ and CD45RO+ T cell subtypes, migrated lymphocytes in the lower chamber were three-color stained with fluorescent mAbs to CD45RA, CD45RO, and CD3. Numbers of CD3+CD45RA+ or CD3+CD45RO+ cells were counted for 20 s, or each cell population was collected to 10,000 events by FACscan for immunophenotyping of migrated and input cells. For counting CD4+ or CD8+ T cell subtypes by FACscan, cells migrated to the lower chamber were stained with mAbs to CD4 and CD8 Ags. For granulocytes, 5 x 105 peripheral blood cells after RBC lysis were added to the upper chamber of Costar Transwell (6.5 mm diameter, 3 µm pore size, polycarbonate membrane) and allowed 90 min for migration. Migrated granulocytes, obtained by collecting suspended cells and detaching adherent cells from the bottom of wells, were counted for 20 s by forward and side-scatter gating to exclude lymphocytes and monocytes. Each chemotaxis experiment was performed in duplicate. All data were analyzed by Student’s t test for significance (p < 0.05), and representative results of at least three independent experiments were obtained.
Calcium flux responses in lymphocytes
Lymphocytes depleted of granulocytes and monocytes were freshly purified from peripheral blood buffycoat for each experiment (see above for details). Cells washed with PBS were loaded with 2.5 µM FURA-2 AM in HBSS (Sigma Chemical Co., St. Louis, MO, pH 7.4) supplemented with 0.05% BSA at 37°C for 45 min, and washed twice with PBS. FURA-2 AM-loaded cells were resuspended in HBSS supplemented with 0.05% BSA at 5 x 106 cells/ml, and placed in a continuously stirred cuvette at 37°C in a MSIII fluorometer (Photon Technology, South Brunswick, NJ). Fluorescence was monitored at 340 and 380 nm for excitation and 510 nm for emission. The data were recorded as the relative ratio of fluorescence excited at 340 and 380 nm. Data were collected every second.
Actin polymerization assay
T cells were resuspended in RPMI 1640 supplemented with 0.1%
BSA at 1.25 x 106 cells/ml. CKß-11/MIP-3ß/ELC was
added at the indicated concentration to the cell solution, and at
15 s post-treatment with CKß-11/MIP-3ß/ELC (the 15-s time
point was found to be the peak time point for actin polymerization by
CKß-11/MIP-3ß/ELC in preliminary experiments), 0.4 ml of cell
solution was transferred to 0.1 ml of FITC-labeled phalloidin solution
(4 x 10-7 M FITC-labeled phalloidin, 0.5 mg/ml
1--lysophosphatidylcholine, and 18% formaldehyde in PBS, all from
Sigma Chemical Co.) to stain and fix cells. Cells were incubated for 10
min, pelleted, and resuspended in 0.5 ml of 1% paraformaldehyde
solution. Mean fluorescence was measured by FACscan.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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CKß-11/MIP-3ß/ELC showed potent chemotactic activity toward
peripheral blood lymphocytes (Table I
).
Maximal attraction at the concentrations assessed was observed at
CKß-11/MIP-3ß/ELC concentrations between 200 and 2000 ng/ml.
Chemokinetic activity, defined as a random movement induced by
chemoattractants in a zero gradient (containing equal amounts of
starting chemoattractant in both chambers), was low (Table I). We
stained the migrated lymphocytes with anti-CD3 Ab to specifically
count T cells and rule out the effect of CKß-11/MIP-3ß/ELC on non-T
cells. MIP-1 and MCP-1 were often too weak to attract T cells
significantly, while CKß-11/MIP-3ß/ELC attracted approximately 90%
of input T cells (Fig. 1).
CKß-11/MIP-3ß/ELC attracted both CD4+CD8-
and CD4-CD8+ T cells better than other
chemokines such as MCP-1 and MIP-1 (Fig. 2). Although, CKß-11/MIP-3ß/ELC is an
efficacious chemoattractant for both CD4+ helper and
CD8+ cytotoxic T cells, the chemotactic activity for
CD4+ cells (78% maximum net migration over background) was
slightly greater than for CD8+ cytotoxic T cells (58%
maximum net migration) (Fig. 2, A and B).
CKß-11/MIP-3ß/ELC demonstrated strong chemotactic activity for
CD45RA+ and CD45RO+ T cells with no significant
preference for either subtype, while consistent with reports of others
(23, 24), MCP-1 and MIP-1 showed preference for CD45RO+
cells with optimum concentrations, 10 to 1000 ng/ml for MCP-1 and 100
to 1000 ng/ml for MIP-1 (Fig. 3, A, B, and
C).
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IL-8, Gro-, and MIP-1 have been reported to attract B cells
(25, 26). To specifically monitor CD19+ B cell migration in
response to chemokines, we stained input and migrated cells with
fluorescent Abs to CD3 and CD19 and counted
CD3-CD19+ cells. CKß-11/MIP-3ß/ELC usually
attracted 15 to 30% of input CD3-CD19+ B
cells at chemokine concentrations between 10 and 100 ng/ml (Fig. 4A). This was a stronger
attraction than that for MIP-1. We examined the effect of
CKß-11/MIP-3ß/ELC on immature CD34+CD19+
pro/pre-B cell progenitors in bone marrow and found that it had no
activity on these cells (data not shown). We used also mAb to sIgM to
examine chemotactic activity of CKß-11/MIP-3ß/ELC on differentiated
B cells because sIgM is expressed on differentiated B cells, but not on
pro/pre-B cells, while CD19 is broadly expressed from pro/pre-B cells
to differentiated B cells (27). CKß-11/MIP-3ß/ELC attracted
sIgM+CD19+ B cells demonstrating its
activity on these differentiated B cells (data not shown). It had
been shown that CKß-11/MIP-3ß/ELC binds EBI1/BLR2/CCR7 (18) and
EBI1/BLR2/CCR7-specific mRNA was detected in all EBV-positive B cell
lines (28). It had been reported that the transcription of the
EBI1/BLR2/CCR7 gene was specifically induced in EBV-negative
cells by estrogen-mediated activation of EBV nuclear Ag 2 (28). In this
regard, we examined the chemotactic effect of CKß-11/MIP-3ß/ELC on
an EBV-transformed B cell line, Priess. Consistent with reports on
expression of EBI1/BLR2/CCR7 mRNA in EBV-transformed cell line (28), we
observed that Priess cells were attracted to CKß-11/MIP-3ß/ELC in a
dose-dependent fashion (Fig. 4B). Priess cells were quite
motile by themselves, which resulted in a high background migration.
This background level of migration into the lower chamber was decreased
by adding CKß-11/MIP-3ß/ELC into the upper chamber forming a
negative gradient of CKß-11/MIP-3ß/ELC (Fig. 4B).
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C) and bone marrow (Fig. 4D) monocytes. Primary chemoattractants for neutrophils are
the CXC chemokines such as IL-8, GRO-, -ß, -
, ENA78, and GCP-2,
all of which have an ELR amino acid sequence motif N-terminal to the
CXC amino acid sequence. CC chemokines and some CXC chemokines, such as
SDF-1 that have no Glu-Leu-Arg (ELR) motif, have no chemotactic
activity for neutrophils (3, 15, 29, 30). Like most other CC
chemokines, CKß-11/MIP-3ß/ELC showed no chemotactic activity for
granulocytes (Fig. 4E). Many chemokines are highly conserved
across species. An extreme example is the SDF-1, which differs in only
one amino acid between mouse and human, and mouse SDF-1 is active on
human leukocytes (15). Although the mouse counterpart of
CKß-11/MIP-3ß/ELC has not been identified, human
CKß-11/MIP-3ß/ELC attracted mouse splenocytes demonstrating its
cross-species activity (Fig. 4F). Pertussis toxin-sensitive CKß-11/MIP-3ß/ELC-dependent chemotaxis and actin polymerization by CKß-11/MIP-3ß/ELC
All chemokines use receptors with seven-transmembrane spanning
domains, which are known to be coupled to trimeric G proteins.
Bordetella pertussis toxin is known to inhibit signaling
from a Gi protein-coupled receptor (31). Pertussis toxin
demonstrated dose response inhibition of chemotaxis in response to
CKß-11/MIP-3ß/ELC (Fig. 5A) indicating
that, like other chemokine receptors, CKß-11/MIP-3ß/ELC signaling
for chemotaxis of cells is transmitted through heterotrimeric
Gi proteins, which are coupled to seven
transmembrane-spanning chemokine receptors, most likely EBI1/BLR2/CCR7
(18, 28, 32, 33).
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B). EC50 for actin polymerization
was observed at about 30 ng/ml CKß-11/MIP-3ß/ELC and optimum
effects were observed at concentrations 
100 ng/ml. The starting point
of the optimum concentration range for actin polymerization by
CKß-11/MIP-3ß/ELC was similar to that for chemotaxis. Calcium mobilization in lymphocytes by CKß-11/MIP-3ß/ELC
Chemokine binding to G protein-coupled seven
transmembrane-spanning receptors induces calcium mobilization. It is
known that phospholipase C ß2 is involved in generation of inositol
triphosphate upon IL-8 binding to its receptor, CXCR1, resulting in
intracellular calcium release (34, 35). We observed that
CKß-11/MIP-3ß/ELC induced calcium mobilization in lymphocytes. This
was stronger and more prolonged than that induced by MIP-1 and
RANTES at the same concentration (Fig. 6). Calcium mobilization by
CKß-11/MIP-3ß/ELC was not desensitized by MIP-1 or RANTES. In
addition, calcium mobilization by either MIP-1 or RANTES was not
desensitized by CKß-11/MIP-3ß/ELC. This cross-desensitization
experiment implies that CKß-11/MIP-3ß/ELC does not use the
receptors for MIP-1 and RANTES, which have been reported to share
receptors CCR1, CCR4, and CCR5, and supports the previous report that
it does not bind these CC chemokine receptors (18). SDF-1 also induced
calcium flux in lymphocytes (Fig. 6). SDF-1-pretreatment desensitized
calcium mobilization by CKß-11/MIP-3ß/ELC completely, while
CKß-11/MIP-3ß/ELC did not desensitize SDF-1-induced calcium
mobilization.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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(25.7%) (37), RANTES (29.4%) (38), and MIP-1ß (29.0%) (39) (Table II). CKß-11/MIP-3ß/ELC forms an
isolated subfamily of the CC chemokine superfamily with another
chemokine, Exodus-1/CKß-4 (40).
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, 2, 3, and 4,
A and B) and is produced by activated macrophages
(17), CKß-11/MIP-3ß/ELC may be important in colocalization of T and
B cells in secondary lymphoid tissues for their interaction.
SDF-1 attracted about 10-fold more lymphocytes than other
chemoattractants such as MCP-1, MIP-1, IL-8, and RANTES (15).
CKß-11/MIP-3ß/ELC shows a similar efficacy to the CXC chemokine,
SDF-1, in attracting T cells. SDF-1 is a strong chemoattractant, but
not a selective chemoattractant for subtypes of T cells in that it
attracts CD45RA-, CD45RO-, CD4-, and CD8-expressing T cells (15).
CKß-11/MIP-3ß/ELC was also not selective in attracting T cell
subtypes except that it had a consistently slightly greater attraction
for CD4+ than CD8+ T cells. The chromosomal
locations of human SDF-1 (44) and CKß-11/MIP-3ß/ELC (18) are 10 and
9, respectively, while most other CXC and CC chemokines are clustered,
with a few exceptions, on chromosomes 4 and 17, respectively. Both
SDF-1 and CKß-11/MIP-3ß/ELC are distantly related in primary amino
acid sequence to other CC and CXC chemokines. The different chromosomal
locations and DNA sequence structures of these two chemokine genes may
suggest that these genes have duplicated and evolved earlier than many
chemokine genes clustering on chromosomes 4 and 17. Both chemokines
were potent in inducing calcium mobilization. SDF-1 desensitizes
calcium mobilization by CKß-11/MIP-3ß/ELC, while
CKß-11/MIP-3ß/ELC does not desensitize SDF-1-dependent calcium
mobilization showing a dominance of SDF-1 over CKß-11/MIP-3ß/ELC in
calcium mobilization in lymphocytes. This is unusual in that SDF-1 is a
CXC chemokine whereas CKß-11/MIP-3ß/ELC is a CC chemokine. This
could be due to two possibilities: 1) SDF-1 may bind EBI1/BLR2/CCR7,
whereas CKß-11/MIP-3ß/ELC may not bind CXCR4, the receptor for
SDF-1; or 2) heterologous cross-desensitization between CXCR4 and
EBI1/BLR2/CCR7 may exist. This latter possibility has recently been
demonstrated for the IL-8, C5a, and FMLP receptors on human neutrophils
(45). Two potent T cell chemoattractants may chemotactically interact
with each other to regulate T cell trafficking by cooperating in
attraction and desensitizing the other’s signaling.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Hal E. Broxmeyer, Department of Microbiology/Immunology and the Walther Oncology Center, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202.
3 Abbreviations used in this paper: MIP, macrophage inflammatory protein; PE, phycoerythrin; MCP-1, monocyte chemoattractant protein-1; CCR, CC chemokine receptor; SDF-1, stromal cell-derived factor 1; ELC, EBI1-ligand chemokine; BLR, Burkitt’s lymphoma receptor; sIgM, surface immunoglobulin M; CHO, Chinese hamster ovary; MALDI, matrix-assisted laser desorption ionized; ELR, Glu-Leu-Arg.
Received for publication July 22, 1997. Accepted for publication November 10, 1997.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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S.-C. Chen, M. W. Leach, Y. Chen, X.-Y. Cai, L. Sullivan, M. Wiekowski, B. J. Dovey-Hartman, A. Zlotnik, and S. A. Lira Central Nervous System Inflammation and Neurological Disease in Transgenic Mice Expressing the CC Chemokine CCL21 in Oligodendrocytes J. Immunol., February 1, 2002; 168(3): 1009 - 1017. [Abstract] [Full Text] [PDF]
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R. T. Palframan, S. Jung, G. Cheng, W. Weninger, Y. Luo, M. Dorf, D. R. Littman, B. J. Rollins, H. Zweerink, A. Rot, et al. Inflammatory Chemokine Transport and Presentation in HEV: A Remote Control Mechanism for Monocyte Recruitment to Lymph Nodes in Inflamed Tissues J. Exp. Med., November 5, 2001; 194(9): 1361 - 1374. [Abstract] [Full Text] [PDF]
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B. Dubois, C. Massacrier, and C. Caux Selective attraction of naive and memory B cells by dendritic cells J. Leukoc. Biol., October 1, 2001; 70(4): 633 - 641. [Abstract] [Full Text] [PDF]
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S.-A. Kellermann and L. M. McEvoy The Peyer's Patch Microenvironment Suppresses T Cell Responses to Chemokines and Other Stimuli J. Immunol., July 15, 2001; 167(2): 682 - 690. [Abstract] [Full Text] [PDF]
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C. H. Kim, L. S. Rott, I. Clark-Lewis, D. J. Campbell, L. Wu, and E. C. Butcher Subspecialization of Cxcr5+ T Cells: B Helper Activity Is Focused in a Germinal Center-Localized Subset of Cxcr5+ T Cells J. Exp. Med., June 18, 2001; 193(12): 1373 - 1382. [Abstract] [Full Text] [PDF]
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E. Lindhout, J. L. M. Vissers, F. C. Hartgers, R. J. F. Huijbens, N. M. Scharenborg, C. G. Figdor, and G. J. Adema The Dendritic Cell-Specific CC-Chemokine DC-CK1 Is Expressed by Germinal Center Dendritic Cells and Attracts CD38-Negative Mantle Zone B Lymphocytes J. Immunol., March 1, 2001; 166(5): 3284 - 3289. [Abstract] [Full Text] [PDF]
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M. Brandes, D. F. Legler, B. Spoerri, P. Schaerli, and B. Moser Activation-dependent modulation of B lymphocyte migration to chemokines Int. Immunol., September 1, 2000; 12(9): 1285 - 1292. [Abstract] [Full Text] [PDF]
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E. P. Bowman, J. J. Campbell, D. Soler, Z. Dong, N. Manlongat, D. Picarella, R. R. Hardy, and E. C. Butcher Developmental Switches in Chemokine Response Profiles during B Cell Differentiation and Maturation J. Exp. Med., April 17, 2000; 191(8): 1303 - 1318. [Abstract] [Full Text] [PDF]
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S. E. Braun, K. Chen, R. G. Foster, C. H. Kim, R. Hromas, M. H. Kaplan, H. E. Broxmeyer, and K. Cornetta The CC Chemokine CK{beta}-11/MIP-3{beta}/ELC/Exodus 3 Mediates Tumor Rejection of Murine Breast Cancer Cells Through NK Cells J. Immunol., April 15, 2000; 164(8): 4025 - 4031. [Abstract] [Full Text] [PDF]
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J. V. Stein, A. Rot, Y. Luo, M. Narasimhaswamy, H. Nakano, M. D. Gunn, A. Matsuzawa, E. J. Quackenbush, M. E. Dorf, and U. H. von Andrian The Cc Chemokine Thymus-Derived Chemotactic Agent 4 (Tca-4, Secondary Lymphoid Tissue Chemokine, 6ckine, Exodus-2) Triggers Lymphocyte Function-Associated Antigen 1-Mediated Arrest of Rolling T Lymphocytes in Peripheral Lymph Node High Endothelial Venules J. Exp. Med., January 3, 2000; 191(1): 61 - 76. [Abstract] [Full Text] [PDF]
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R.A. Warnock, J.J. Campbell, M.E. Dorf, A. Matsuzawa, L.M. McEvoy, and E.C. Butcher The Role of Chemokines in the Microenvironmental Control of T versus B Cell Arrest in Peyer's Patch High Endothelial Venules J. Exp. Med., January 3, 2000; 191(1): 77 - 88. [Abstract] [Full Text] [PDF]
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H. Hasegawa, T. Nomura, M. Kohno, N. Tateishi, Y. Suzuki, N. Maeda, R. Fujisawa, O. Yoshie, and S. Fujita Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells Blood, January 1, 2000; 95(1): 30 - 38. [Abstract] [Full Text] [PDF]
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H. D. Byrnes, H. Kaminski, A. Mirza, G. Deno, D. Lundell, and J. S. Fine Macrophage Inflammatory Protein-3{beta} Enhances IL-10 Production by Activated Human Peripheral Blood Monocytes and T Cells J. Immunol., November 1, 1999; 163(9): 4715 - 4720. [Abstract] [Full Text] [PDF]
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K. M. Ansel, L. J. McHeyzer-Williams, V. N. Ngo, M. G. McHeyzer-Williams, and J. G. Cyster In Vivo-Activated Cd4 T Cells Upregulate Cxc Chemokine Receptor 5 and Reprogram Their Response to Lymphoid Chemokines J. Exp. Med., October 18, 1999; 190(8): 1123 - 1134. [Abstract] [Full Text] [PDF]
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C. H. Kim, C.-K. Qu, G. Hangoc, S. Cooper, N. Anzai, G.-S. Feng, and H. E. Broxmeyer Abnormal Chemokine-Induced Responses of Immature and Mature Hematopoietic Cells from Motheaten Mice Implicate the Protein Tyrosine Phosphatase Shp-1 in Chemokine Responses J. Exp. Med., September 6, 1999; 190(5): 681 - 690. [Abstract] [Full Text] [PDF]
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L. Ottonello, A. Corcione, G. Tortolina, I. Airoldi, E. Albesiano, A. Favre, R. D'Agostino, F. Malavasi, V. Pistoia, and F. Dallegri rC5a Directs the In Vitro Migration of Human Memory and Naive Tonsillar B Lymphocytes: Implications for B Cell Trafficking in Secondary Lymphoid Tissues J. Immunol., June 1, 1999; 162(11): 6510 - 6517. [Abstract] [Full Text] [PDF]
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R. Krzysiek, E. A. Lefevre, W. Zou, A. Foussat, J. Bernard, A. Portier, P. Galanaud, and Y. Richard Antigen Receptor Engagement Selectively Induces Macrophage Inflammatory Protein-1{alpha} (MIP-1{alpha}) and MIP-1{beta} Chemokine Production in Human B Cells J. Immunol., April 15, 1999; 162(8): 4455 - 4463. [Abstract] [Full Text] [PDF]
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S.-A. Kellermann, S. Hudak, E. R. Oldham, Y.-J. Liu, and L. M. McEvoy The CC Chemokine Receptor-7 Ligands 6Ckine and Macrophage Inflammatory Protein-3{beta} Are Potent Chemoattractants for In Vitro- and In Vivo-Derived Dendritic Cells J. Immunol., April 1, 1999; 162(7): 3859 - 3864. [Abstract] [Full Text] [PDF]
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M. D. Gunn, S. Kyuwa, C. Tam, T. Kakiuchi, A. Matsuzawa, L. T. Williams, and H. Nakano Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization J. Exp. Med., February 1, 1999; 189(3): 451 - 460. [Abstract] [Full Text] [PDF]
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V. N. Ngo, H. Korner, M. D. Gunn, K. N. Schmidt, D. Sean Riminton, M. D. Cooper, J. L. Browning, J. D. Sedgwick, and J. G. Cyster Lymphotoxin {alpha}/{beta} and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen J. Exp. Med., January 18, 1999; 189(2): 403 - 412. [Abstract] [Full Text] [PDF]
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C. H. Kim, L. M. Pelus, J. R. White, and H. E. Broxmeyer Macrophage-Inflammatory Protein-3{beta}/EBI1-Ligand Chemokine/CK{beta}-11, a CC Chemokine, Is a Chemoattractant with a Specificity for Macrophage Progenitors Among Myeloid Progenitor Cells J. Immunol., September 1, 1998; 161(5): 2580 - 2585. [Abstract] [Full Text] [PDF]
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M.-C. Dieu, B. Vanbervliet, A. Vicari, J.-M. Bridon, E. Oldham, S. Ait-Yahia, F. Briere, A. Zlotnik, S. Lebecque, and C. Caux Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites J. Exp. Med., July 20, 1998; 188(2): 373 - 386. [Abstract] [Full Text] [PDF]
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C. H. Kim, L. M. Pelus, J. R. White, and H. E. Broxmeyer Differential Chemotactic Behavior of Developing T Cells in Response to Thymic Chemokines Blood, June 15, 1998; 91(12): 4434 - 4443. [Abstract] [Full Text] [PDF]
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