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CHEMOKINES
From the Departments of Infectious Diseases and
Microbiology, Molecular Genetics and Biochemistry, and Biostatistics,
University of Pittsburgh, Pittsburgh, PA.
Chemokines are important mediators of cell trafficking during
immune inductive and effector activities, and dysregulation of their
expression might contribute to the pathogenesis of human immunodeficiency virus type 1 and the related simian immunodeficiency virus (SIV). To understand better the effects of SIV infection on
lymphoid tissues in rhesus macaques, we examined chemokine messenger
RNA (mRNA) expression patterns by using DNA filter array hybridization.
Of the 34 chemokines examined, the interferon The ultimate consequences of the immune destructive
effects of human immunodeficiency virus 1 (HIV-1) are well
described,1 but the precise mechanisms by which immune
function is progressively lost during the course of infection remain
incompletely understood. To develop new strategies for combating the
pathogenic effects of HIV-1 infection, it is crucial to obtain a better
understanding of the effects of the virus on local lymphoid tissues in
vivo. Central to immune inductive and effector activities is the
trafficking of antigen-presenting cells (APCs), naïve T and B
lymphocytes, and effector lymphocytes.2 Among the
components critical for cellular trafficking events required for
appropriate induction of immune responses are chemokines, which are
small (8-10 kd) cytokines chemotactic for cells bearing the appropriate
G-protein-coupled receptor.3 This idea has been
underscored through studies of antigen-presenting dendritic cells (DCs)
showing that during DC maturation, a switch in chemokine receptor
expression from CC chemokine receptor (CCR) 6 to CCR7 occurs concordant
with a change in chemotactic responsiveness of the DCs from CC
chemokine ligand (CCL) 20/macrophage inflammatory protein (MIP)-3 To determine whether levels of chemokine expression change during the
course of pathogenic simian immunodeficiency virus (SIV) infection, we
used DNA array hybridization to quantitate the relative expression
levels of 34 chemokine messenger RNAs (mRNAs) in spleen tissues during
different stages of disease. The most highly induced chemokine was the
inflammatory chemokine CXC chemokine ligand 9/monokine induced by
interferon- Macaques and tissues
DNA array hybridization and analyses
RT-PCR, subcloning, and sequencing of rhesus macaque CXCL9/Mig Rhesus macaque CXCL9/Mig partial cDNA was obtained by RT-PCR amplification of macaque lung total RNA with primers TRMigF (5'-ATGAAGAAAAGTGGTGTTCTT-3') and TRMigR (5'-AAGTGGTCTCTTATGTAGTCTT-3'). PCR products were ligated to the pGEM-T vector (Promega, Madison, WI) and the DNA was sequenced (GenBank accession number AY044445). Comparison of the deduced amino acid sequences of the rhesus macaque and human CXCL9/Mig cDNAs showed 92.8% identity.In situ hybridization ISHs were done as described previously,8,9 except that tissue pretreatments consisted of microwaving in 0.01 M citrate buffer (pH 6.0) followed by acetylation in 0.25% acetic anhydride and 0.1 M triethanolamine and hybridization was done at 50°C. ISHs simultaneously using sulfur 35 (35S)-labeled and digoxigenin 11-uridine triphosphate-labeled probes were done identically, except that all dithiothreitol (DTT) concentrations were 10 mM. Sections were then rinsed for 2 minutes in Tris-buffered saline (TBS; 0.1 M Tris [pH 7.5]) and blocked overnight at 4°C in TBS, 3% blocking agent (Roche, Indianapolis, IN), and 3% nonfat dry milk. Digoxigenin-labeled riboprobe was detected with an antidigoxigenin antibody conjugated to alkaline phosphatase (1:500; 4-hour incubation; Roche) according to the manufacturer's recommendations. After incubation with 5-bromo-4-chloro-3-indolylphosphate and nitroblue tetrazolium for 4 hours, sections were rinsed in TBS, dehydrated, air dried, and subjected to emulsion autoradiography with exposure times of 1 to 2 days. Simultaneous immunohistochemical staining and ISHs were done as described previously,8,9 except that all DTT concentrations were reduced to 10 mM.Quantitative image analysis ISH signals for CXCL9/Mig were quantitated by using a quantitative image capture and analysis system as described previously.8 The system employed a SPOT digital camera (Diagnostic Instruments, Sterling Heights, MI) mounted on a Nikon E600 microscope fitted with a 20× Plan Apochromat objective and an IGS polarizing filter cube (Omega Optical, Brattleboro, VT). Images were captured and analyzed with Metaview software (Universal Imaging, West Chester, PA).Real-time RT-PCR 5' fluorogenic nuclease assay Real-time RT-PCR was done with a 2-step protocol as described previously.10 Total RNAs were obtained from snap-frozen tissue specimens by using Trizol, treated with deoxyribonuclease (Ambion, Dallas, TX), and purified with RNeasy columns (Qiagen, Valencia, CA). For each specimen, 400 ng and 100 ng RNA were separately reverse transcribed by using random hexamers and Superscript II RT (Life Technologies) in a 100-µL reaction. RT-negative controls were obtained with 400 ng of each RNA. PCR amplification used 5 µL of each cDNA at empirically determined optimal concentrations of forward and reverse primers and 6-carboxyfluorescein (FAM)-labeled Taqman probe. The following primer and probe concentrations were used for amplification and detection of specific mRNAs. CXCL9/Mig mRNA primers were used at 300 nM each and FAM/6-carboxy-N,N,N', N'-tetramethylrhodamine (TAMRA)-labeled probe was used at 200 nM; -glucuronidase ( -GUS) primers and FAM/TAMRA-labeled probe were
all used at 100 nM each; and IFN- primers were used at 200 nM and
FAM/TAMRA-labeled probe was used at 100 nM. The PCR reactions were
cycled at 95°C for 12 minutes followed by 40 cycles at 95°C for 15 seconds and at 60°C for 1 minute on an ABI Prism 7700 Sequence Detection System (PE Applied Biosystems, Foster City, CA).
The CXCL9/Mig and IFN- Relative quantitation of CXCL9/Mig mRNA expression levels was
calculated by using the comparative CT
method,10,11 with the Determinations of plasma viral load Virion-associated RNA in plasma was measured by using Taqman real-time RT-PCR with an external standard curve.57Statistical analyses All statistical analyses were done with Minitab software (State College, PA). Data from the Mig ISH experiments were analyzed by repeated measures analysis of variance (ANOVA). Data from the IFN-
ISH and the CXCR3 flow cytometry experiments were analyzed by using a
nonparametric equivalent to a one-way ANOVA (Kruskal-Wallis test) when
comparisons were made between groups of different macaques. For
analysis of changes in CXCR3 expression levels at different times PI in
the same group of macaques, data were checked for the normality of the
paired differences and a paired t test was then performed.
Reported P values were not adjusted for multiple comparisons. Real-time RT-PCR data were analyzed by using a
t test.
Array hybridization identifies CXCL9/Mig up-regulation in spleen To examine patterns of expression of chemokine mRNA in lymphoid tissues of rhesus macaques infected with SIV, we obtained spleen tissues from macaques infected with the pathogenic SIV/ B670 isolate6 and determined chemokine mRNA expression levels by using DNA filter array hybridization. The macaques included in these
studies represented different stages of SIV-associated disease, ranging
from acute infection to AIDS (Table 1).
We extracted total RNAs from snap-frozen specimens, pooled them by
disease state, generated phosphorus 33 (33P)-labeled cDNA
probes, and hybridized them to commercially available DNA filter arrays
(Figure 1). The signal-intensity values
represented the mean of the intensity values for the duplicate spots
for each gene after subtraction of local background and normalization
against the mean of the intensity values of the 9 housekeeping genes
(Figure 1B) on each filter. The relative levels of expression of the
chemokine mRNAs are listed in Table 2 in
the order of greatest to least signal intensity for the AIDS pool.
Ratios of 2.0 or greater that included at least one normalized value
greater than 0.2 are noted.
Of the 34 chemokine mRNAs examined, 21 had relatively constant levels
of expression throughout infection (ratios, 0.5 to 1.9), including
6Ckine/CCL21, which is involved in the recruitment of mature or
maturing DCs4 and naïve and central memory T
lymphocytes.12 Eleven chemokine mRNAs, including
MIP-1 SIV infection alters CXCL9/Mig expression patterns and levels in macaque lymphoid tissues We next focused our analyses on expression of CXCL9/Mig mRNA because CXCL9/Mig is an inflammatory chemokine that is induced by the type 1 cytokine IFN- 13 and because increases in its expression have been observed in chronic inflammatory
diseases.5 We examined the expression patterns of
CXCL9/Mig in greater detail directly in tissues from individual
macaques. ISH with a 35S-labeled rhesus macaque
CXCL9/Mig-specific riboprobe confirmed that the levels of expression of
CXCL9/Mig mRNA were much lower in spleen and lymph node tissues from
uninfected macaques (Figures 2A and 2B)
than in tissues from macaques with acute infections (Figures 2C and 2D)
or AIDS (Figures 2E and 2F). In spleens of uninfected macaques, rare
CXCL9/Mig mRNA-positive (mRNA+) cells were predominantly in
the macrophage-rich red pulp. Such cells were also present during acute
infection, but there was also a dramatic increase in the ISH signals in
the periarteriolar lymphoid sheaths in the white pulp (Figure 2C). In
animals with AIDS, the pattern of expression changed further, to
include cells in germinal centers and marginal zones (Figure 2E). In
lymph nodes, increased levels of expression of CXCL9/Mig during acute
infection and AIDS were observed in T-lymphocyte-rich paracortical
regions, with some increased expression in medullary regions (Figures
2D and 2F).
We quantitated the ISH signals for CXCL9/Mig mRNA by using image
capture and analysis,8 whereby the surface area of
epipolarized light reflected by silver grains can be thresholded and
measured. Ten randomly chosen microscopical fields were examined from
each tissue section hybridized with the antisense riboprobe and are presented in Figure 3A as
background-corrected individual data points. The signals obtained after
ISH to uninfected macaque spleen tissues with the CXCL9/Mig riboprobe
were extremely low (mean surface area of reflected light, 1773 µm2; Figure 3A), whereas the ISH signals for CXCL9/Mig
mRNA in spleen tissues from animals with acute infection or AIDS were
significantly higher (P = .005 and P < .001,
respectively; mean values, 10 251 µm2 and 16 800
µm,2 respectively; Figure 3A). To further assess the
differences in expression of CXCL9/Mig mRNA, we developed a real-time
RT-PCR assay specific for CXCL9/Mig. Using this approach, we found that
the levels of CXCL9/Mig mRNA expression were also significantly higher
during acute infection and AIDS (P = .02 and
P = .044, respectively; mean increases, 6.5 and 11.2 fold, respectively, over values in the uninfected macaque used for
calibration [M6600]; Figure 3B).
Lymph node specimens were obtained from macaques before infection with
SIV/
Increased levels of expression of CXCL9/Mig mRNA (Figures 1-4) were
associated with increased levels of local and systemic SIV/ CXCL9/Mig mRNA+ cells colocalize with SIV-positive cells in lymphoid tissues To examine the spatial relations among cells expressing CXCL9/Mig and SIV mRNAs, we conducted simultaneous ISHs for CXCL9/Mig mRNA with a 35S-labeled riboprobe and for SIV RNA with digoxigenin-labeled riboprobes. This strategy revealed that productively infected cells did not express appreciable levels of CXCL9/Mig mRNA (Figures 5B and 5F). However, SIV RNA+ cells were localized predominantly in microanatomical regions that also contained CXCL9/Mig mRNA (Figures 5A, 5B, 5E, and 5F). Classification of the immediate local environment of SIV RNA+ cells as either abundant for or devoid of CXCL9/Mig mRNA on the basis of the control sense riboprobe hybridization showed that 84% of SIV RNA+ cells were localized in areas with abundant CXCL9/Mig mRNA expression.
To identify the populations of cells expressing the increased amounts
of CXCL9/Mig mRNA, we conducted ISH for CXCL9/Mig mRNA simultaneously
with immunohistochemical staining for the monocyte/macrophage marker
CD68 (Figures 5D and 5H). Only a proportion of CXCL9/Mig mRNA+ cells were also CD68+. We also identified
and enumerated IFN- Reduced levels of CXCR3 on CD3+ and CD8+ peripheral blood cells during SIV infection To determine whether the high levels of expression of CXCL9/Mig in lymphoid tissues affected the expression of its receptor, CXCR3,14 in peripheral blood, we conducted 2-color flow cytometry analyses of cryopreserved peripheral blood mononuclear cells with gating on CD3+ or CD8+ lymphocytes. CXCR3 is also a receptor for CXCL10/IFN-inducible protein 10 (IP-10) and CXCL11/IFN-inducible T-cell -chemoattractant (I-TAC); it is found on
effector T lymphocytes as well as on T lymphocytes recently activated
in the presence of interleukin 2,14 and its expression has
been associated with a type 1 cytokine production
profile.18-21 The percentages of CD3+
lymphocytes and CD8+ lymphocytes that were
CXCR3+ were higher in uninfected macaques than in infected
macaques (Figure 6). Although these data
indicate an overall trend toward reduced CXCR3 expression of
CD3+ and CD8+ lymphocytes after SIV infection,
the differences between findings in uninfected macaques and infected
animals were not significant (P values, .064 to .355).
However, results of paired sample comparisons of preinfection and
necropsy values for CXCR3 expression on CD3+ lymphocytes
during acute infection were significantly different (P = .005; Figure 6). Of note, the percentages of
CXCR3+/CD3+ and
CXCR3+/CD8+ lymphocytes from M5599, which had
only minimal SIV replication (Table 1) and CXCL9/Mig induction (Figures
3 and 4), were among the highest in the acutely infected animals
(Figure 6). These data therefore indicated that there was an
association between the increased CXCL9/Mig expression in secondary
lymphoid tissues and reduced CXCR3 expression on peripheral blood T
lymphocytes.
Chemokines are small chemoattractant cytokines that recruit cells
into microenvironments as part of constitutive and inflammatory trafficking events.2,3 Trafficking of cells to specific
microanatomical compartments is important for immune inductive and
effector activities, since APCs, naïve T lymphocytes, and
effector T lymphocytes must move from one environment to another.
Although the exact mechanisms by which HIV-1 and SIV cause immunologic
dysfunction leading to AIDS remain incompletely understood,
inappropriate trafficking or homing of cell populations to secondary
lymphoid tissues might play a significant role.22 In this
study, we demonstrated that during infection of rhesus macaques with
pathogenic SIV, changes occur in the levels of expression of mRNAs
encoding chemokines in lymphoid tissues and that some of these changes
are evident within 2 weeks PI. Of the 34 chemokine mRNAs examined by
means of DNA filter array hybridization, CXCL9/Mig and CXCL13/BLC had the greatest increases in spleens of macaques with AIDS compared with
uninfected controls. We focused our analyses on CXCL9/Mig because it is
an inflammatory chemokine induced by IFN- In-depth ISH and real-time RT-PCR analyses showed a large, significant
increase in the expression of CXCL9/Mig mRNA in spleen and lymph nodes,
which we found to be associated not only with local SIV replication but
also with increased IFN- On the basis of the data presented here, we propose the following model
of chronic inflammation in lymphoid tissues during SIV infection
(Figure 7). First, productive infection
of target cells leads to local SIV-specific cytotoxic T lymphocyte
(CTL) and Th responses, some of which produce IFN-
Predictions based on this model related to HIV-1 infection and
pathogenesis are supported by previous findings. First, similar increases in the expression of CXCR3 ligands would be expected to occur
in individuals infected with HIV-1. Indeed, immunohistochemical studies
showed that IP-10/CXCL10 protein expression is increased in lymph nodes
in individuals positive for HIV-1.34 Second, IFN- The IFN- Increased homing of resting T lymphocytes to secondary lymphoid tissues
and their subsequent loss has been proposed as a mechanism of HIV-1
pathogenesis.22,53,54 The data presented here on the
effects of SIV infection in lymphoid tissues of rhesus macaques are
consistent with such a model, although the CXCR3+ T
lymphocytes we propose as being important in these processes are likely
effector T lymphocytes. Consistent with these models, the biphasic
increase in CD4+ T lymphocyte counts observed in patients
after potent antiretroviral therapy55 might be due partly
to coordinated reductions in expression of IFN- The findings and model described here have strong implications for
current and new-generation therapies and vaccines for HIV-1. They
underscore the importance of potent antiretroviral therapy in
containing the infection because of the role of productively infected
cells in the initiation of the IFN-
We thank Dawn McClemens-McBride, Melanie O'Malley, and Shane
Ritchey for excellent assistance with project coordination and animal
care; Matt Delp for technical assistance; Dr Edward Klein for
assistance in evaluating the histopathological findings; Dr Francois
Villinger for providing the rhesus macaque IFN-
Submitted November 2, 2001; accepted December 14, 2001.
Supported by National Institutes of Health grant R01 HL62056 to T.A.R.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Todd A. Reinhart, Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 606 Parran Hall, 130 DeSoto St, Pittsburgh, PA 15261; e-mail: reinhar{at}pitt.edu.
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© 2002 by The American Society of Hematology.
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I. B. Hogue, S. H. Bajaria, B. A. Fallert, S. Qin, T. A. Reinhart, and D. E. Kirschner The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection J. Gen. Virol., September 1, 2008; 89(9): 2228 - 2239. [Abstract] [Full Text] [PDF] |
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D. Bonneh-Barkay, S. J. Bissel, G. Wang, K. N. Fish, G. C.B. Nicholl, S. W. Darko, R. Medina-Flores, M. Murphey-Corb, P. A. Rajakumar, J. Nyaundi, et al. YKL-40, a Marker of Simian Immunodeficiency Virus Encephalitis, Modulates the Biological Activity of Basic Fibroblast Growth Factor Am. J. Pathol., July 1, 2008; 173(1): 130 - 143. [Abstract] [Full Text] [PDF] |
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S. Qin, Y. Sui, A. C. Soloff, B. A. Fallert Junecko, D. E. Kirschner, M. A. Murphey-Corb, S. C. Watkins, P. M. Tarwater, J. E. Pease, S. M. Barratt-Boyes, et al. Chemokine and Cytokine Mediated Loss of Regulatory T Cells in Lymph Nodes during Pathogenic Simian Immunodeficiency Virus Infection J. Immunol., April 15, 2008; 180(8): 5530 - 5536. [Abstract] [Full Text] [PDF] |
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C. C. Clay, D. S. Rodrigues, Y. S. Ho, B. A. Fallert, K. Janatpour, T. A. Reinhart, and U. Esser Neuroinvasion of Fluorescein-Positive Monocytes in Acute Simian Immunodeficiency Virus Infection J. Virol., November 1, 2007; 81(21): 12040 - 12048. [Abstract] [Full Text] [PDF] |
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P. L. Lin, S. Pawar, A. Myers, A. Pegu, C. Fuhrman, T. A. Reinhart, S. V. Capuano, E. Klein, and J. L. Flynn Early Events in Mycobacterium tuberculosis Infection in Cynomolgus Macaques Infect. Immun., July 1, 2006; 74(7): 3790 - 3803. [Abstract] [Full Text] [PDF] |
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K. Abel, B. Pahar, K. K. A. Van Rompay, L. Fritts, C. Sin, K. Schmidt, R. Colon, M. McChesney, and M. L. Marthas Rapid virus dissemination in infant macaques after oral simian immunodeficiency virus exposure in the presence of local innate immune responses. J. Virol., July 1, 2006; 80(13): 6357 - 6367. [Abstract] [Full Text] [PDF] |
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C. N. Renn, D. J. Sanchez, M. T. Ochoa, A. J. Legaspi, C.-K. Oh, P. T. Liu, S. R. Krutzik, P. A. Sieling, G. Cheng, and R. L. Modlin TLR Activation of Langerhans Cell-Like Dendritic Cells Triggers an Antiviral Immune Response J. Immunol., July 1, 2006; 177(1): 298 - 305. [Abstract] [Full Text] [PDF] |
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C. C. Clay, D. S. Rodrigues, D. J. Harvey, C. M. Leutenegger, and U. Esser Distinct Chemokine Triggers and In Vivo Migratory Paths of Fluorescein Dye-Labeled T Lymphocytes in Acutely Simian Immunodeficiency Virus SIVmac251-Infected and Uninfected Macaques J. Virol., November 1, 2005; 79(21): 13759 - 13768. [Abstract] [Full Text] [PDF] |
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S. K. Sanghavi and T. A. Reinhart Increased Expression of TLR3 in Lymph Nodes during Simian Immunodeficiency Virus Infection: Implications for Inflammation and Immunodeficiency J. Immunol., October 15, 2005; 175(8): 5314 - 5323. [Abstract] [Full Text] [PDF] |
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A. Kouroumalis, R. J. Nibbs, H. Aptel, K. L. Wright, G. Kolios, and S. G. Ward The Chemokines CXCL9, CXCL10, and CXCL11 Differentially Stimulate G{alpha}i-Independent Signaling and Actin Responses in Human Intestinal Myofibroblasts J. Immunol., October 15, 2005; 175(8): 5403 - 5411. [Abstract] [Full Text] [PDF] |
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J. F. Foley, C.-R. Yu, R. Solow, M. Yacobucci, K. W. C. Peden, and J. M. Farber Roles for CXC Chemokine Ligands 10 and 11 in Recruiting CD4+ T Cells to HIV-1-Infected Monocyte-Derived Macrophages, Dendritic Cells, and Lymph Nodes J. Immunol., April 15, 2005; 174(8): 4892 - 4900. [Abstract] [Full Text] [PDF] |
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M. D. George, E. Reay, S. Sankaran, and S. Dandekar Early Antiretroviral Therapy for Simian Immunodeficiency Virus Infection Leads to Mucosal CD4+ T-Cell Restoration and Enhanced Gene Expression Regulating Mucosal Repair and Regeneration J. Virol., March 1, 2005; 79(5): 2709 - 2719. [Abstract] [Full Text] [PDF] |
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Y. Sui, S. Li, D. Pinson, I. Adany, Z. Li, F. Villinger, O. Narayan, and S. Buch Simian Human Immunodeficiency Virus-Associated Pneumonia Correlates with Increased Expression of MCP-1, CXCL10, and Viral RNA in the Lungs of Rhesus Macaques Am. J. Pathol., February 1, 2005; 166(2): 355 - 365. [Abstract] [Full Text] [PDF] |
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N. Kohrgruber, M. Groger, P. Meraner, E. Kriehuber, P. Petzelbauer, S. Brandt, G. Stingl, A. Rot, and D. Maurer Plasmacytoid Dendritic Cell Recruitment by Immobilized CXCR3 Ligands J. Immunol., December 1, 2004; 173(11): 6592 - 6602. [Abstract] [Full Text] [PDF] |
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C. R. Baskin, A. Garcia-Sastre, T. M. Tumpey, H. Bielefeldt-Ohmann, V. S. Carter, E. Nistal-Villan, and M. G. Katze Integration of Clinical Data, Pathology, and cDNA Microarrays in Influenza Virus-Infected Pigtailed Macaques (Macaca nemestrina) J. Virol., October 1, 2004; 78(19): 10420 - 10432. [Abstract] [Full Text] [PDF] |
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K. Abel, L. La Franco-Scheuch, T. Rourke, Z.-M. Ma, V. de Silva, B. Fallert, L. Beckett, T. A. Reinhart, and C. J. Miller Gamma Interferon-Mediated Inflammation Is Associated with Lack of Protection from Intravaginal Simian Immunodeficiency Virus SIVmac239 Challenge in Simian-Human Immunodeficiency Virus 89.6-Immunized Rhesus Macaques J. Virol., January 15, 2004; 78(2): 841 - 854. [Abstract] [Full Text] [PDF] |
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C. L. Fuller, J. L. Flynn, and T. A. Reinhart In Situ Study of Abundant Expression of Proinflammatory Chemokines and Cytokines in Pulmonary Granulomas That Develop in Cynomolgus Macaques Experimentally Infected with Mycobacterium tuberculosis Infect. Immun., December 1, 2003; 71(12): 7023 - 7034. [Abstract] [Full Text] [PDF] |
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B. Vanbervliet, N. Bendriss-Vermare, C. Massacrier, B. Homey, O. de Bouteiller, F. Briere, G. Trinchieri, and C. Caux The Inducible CXCR3 Ligands Control Plasmacytoid Dendritic Cell Responsiveness to the Constitutive Chemokine Stromal Cell-derived Factor 1 (SDF-1)/CXCL12 J. Exp. Med., September 2, 2003; 198(5): 823 - 830. [Abstract] [Full Text] [PDF] |
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Y. K. Choi, B. A. Fallert, M. A. Murphey-Corb, and T. A. Reinhart Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo Blood, March 1, 2003; 101(5): 1684 - 1691. [Abstract] [Full Text] [PDF] |
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C. L. Fuller, Y. K. Choi, B. A. Fallert, S. Capuano III, P. Rajakumar, M. Murphey-Corb, and T. A. Reinhart Restricted SIV Replication in Rhesus Macaque Lung Tissues During the Acute Phase of Infection Am. J. Pathol., September 1, 2002; 161(3): 969 - 978. [Abstract] [Full Text] [PDF] |
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