scholarly journals O10: METFORMIN TREATMENT IMPROVES LYMPHOCYTE METABOLISM IN A MOUSE MODEL OF MAJOR SURGERY

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
TF Jones ◽  
A Gutierrez ◽  
del Arroyo ◽  
SM Henson ◽  
GL Ackland
Keyword(s):  
T Lymphocytes ◽  
Mouse Model ◽  
T Lymphocyte ◽  
Major Surgery ◽  
P Value ◽  
Free Access ◽  
Mitochondrial Bioenergetics ◽  
Metformin Treatment ◽  
Respiratory Capacity

Abstract Introduction Lymphopaenia is common after major surgery and associated with poor outcome. T-lymphocytes restrain damaging innate inflammation. Major surgery impairs T-lymphocyte metabolism in humans, which promotes lymphopaenia. Metformin is known to improve mitochondrial bioenergetics in models of inflammation. Firstly, we hypothesised that a mouse model of major surgery would demonstrate impaired T-lymphocyte metabolism and secondly, that metformin treatment in vivo would reverse the phenotype. Method Male C57Bl/6 mice aged between 8 and 12 weeks were housed in a specific pathogen free environment with free access to food and water. Animals were dosed with either vehicle (phosphate buffered saline, 20 ml/kg) or metformin (250 mg/kg) daily via intraperitoneal injection for four days prior to and after surgery. A partial hepatectomy was performed under isofluorane anaesthesia. Naive littermates were used as controls. All experiments were performed according to the Animals (Scientific Procedures) Act 1986. Splenic T-lymphocytes were isolated by negative selection using magnetic beads. Mitochondrial bioenergetics were measured using a Seahorse Extracellular Flux analyser. Parametric statistical analysis was performed and a p-value < 0.05 was chosen to represent significance. Result T-lymphocytes demonstrated reduced spare respiratory capacity (SRC, 285 vs 497 %, p=0.004) after surgery compared to naive controls. Metformin treatment in vivo reversed this observation and SRC was comparable to naive (437 vs 497 %, p=0.34). Metformin treatment in vitro increased spare respiratory capacity in T-lymphocytes from mice after surgery compared to naive (change from untreated, 187 vs 91 %, p=0.03). Conclusion Perioperative metformin treatment improved T-lymphocyte metabolism in a mouse model of major surgery. Take-home message Metformin is a potential treatment for the lymphocyte metabolic dysfunction observed after surgery.

scholarly journals Performance of the BD FACSPresto near to patient Analyzer in comparison with representative conventional CD4 instruments in Cameroon.

2020 ◽  
Author(s):  
Bertrand Sagnia ◽  
Fabrice MBAKOP Ghomsi ◽  
Ana Gutierrez ◽  
Samuel SOSSO ◽  
Rachel KAMGAING ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Statistical Significance ◽  
P Value ◽  
Resource Constrained ◽  
Inform Consent ◽  
Remote Areas ◽  
Significant Difference ◽  
Sensitivity Specificity ◽  
Cd4 Testing

Abstract Background In the context of scaling the viral load in resource limited settings, following HIV infected patient’s adults and children with CD4+ T-lymphocyte count still very important in settings where the decentralization of treatment still has some challenges. Effective HIV monitoring in these resource-constrained settings needs affordable and reliable CD4+ T lymphocytes enumeration methods. We investigated the validity of a BD FACSPresto POC which is a dedicated system for enumeration that uses immunofluorescent technologies. In this study, we have assessed the sensitivity, specificity and correlation between most representative flow cytometry instruments present in Cameroon with more than 5000 CD4 T cells tests per year including FACSCalibur, FACSCount, and PIMA POC from Becton dinkinson and ALERE respectively. Methods 268 patients aged from 1 to 72 years old were enrolled and included in the study after inform consent. The BD FACSPresto POC CD4+ T cell technology was placed at CIRCB and operated by technician staff. HIV infected patients were from Chantal BIYA international reference Center (CIRCB), Centre de Sante Catholique de NKOLODOM, Centre de Sante Catholique de BIKOP and CASS de Nkolndongo – Yaounde We compared the accuracy of the BD FACSPresto and three existing reference technologies with more than 5000 tests per year like FACSCalibur, FACSCount and PIMA according to the number of CD4 test done per year and their repartition in the country. Bland – Altman method and correlation analysis were used to estimate mean bias and 95% limits of agreement and to compare the methods, including analysis by subgroup of participant gestational age. In addition sensitivity and specificity were determined. Statistical significance was set at p-value < 0.05 Results The BD FACSPresto POC system has excellent precision, accuracy and linearity for CD4+ T lymphocytes enumeration. Good correlations were obtained between the BD FACSPresto poc system and other single platform methods. Bland–Altman plots showed interchangeability between two machines mean bias BD-FACSPresto vs PIMA= -126,522(-161,221 to -91,822) BD-FACSPresto vs FACSCount= -38,708 (-58,935 to -18,482) and FACSPresto vs FACSCALIBUR= 0,791(-11,908 to 13,491). Mean difference with Absolute CD4+ T-lymphocyte values obtained from the BD FACSPresto system correlated well with PIMA, FACSCount, and FACSCalibur method with R 2 equal to 0.88, 0.92 and 0.968 respectively with P < 0.001 for all. The mean comparison between values obtained from BD FACSPresto with PIMA, FACSCount, and FACSCalibur using paired T test give P=0.17, P=0.5 and P=0.6 respectively meaning that there is no significant differences between values obtained with BD FACSPresto and PIMA, FACSCount or FACSCalibur CD4 enumeration machines. Further analysis revealed close agreement between all the three instruments with no significant difference between the forth methods (P=0.91) Conclusion This BD-FACSPresto POC system is a simple, robust and reliable system for enumeration of absolute and percentage of CD4+ T-lymphocytes especially suitable for remote areas with limited resources. Having one BD-FACSPresto POC system easy to use, should reduce the cost and thus increase and improved access to CD4 testing for HIV infected patients in resource-constrained countries. BD-FACSPresto POC CD4 will enable reduction in patient time and improve the overall quality of ART service count and may improve test access in remote areas. This technology can allow for greater decentralization and wider access to CD4 testing and ART

PRMT5 Transgenic Mice Develop Aggressive Lymphoblastic Lymphomas

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2936-2936
Author(s):  
Porsha L. Smith ◽  
Fengting Yan ◽  
John T. Patton ◽  
Lapo Alinari ◽  
Vrajesh Karkhanis ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mouse Model ◽  
Transgenic Mice ◽  
Transgenic Mouse Model ◽  
P Value ◽  
Wild Type ◽  
Over Expression ◽  
Epigenetic Modifier ◽  
F1 Generation

Abstract Introduction: Emerging data collected from whole genome and epigenomic studies in solid and blood cancers has pointed toward dysregulation of chromatin remodelers as a unique class of cancer drivers. Next generation sequencing of lymphoma has identified several mutations affecting enzymes that regulate epigenetic control of gene expression. The epigenetic modifier protein arginine methyltransferase 5 (PRMT5) that has been shown to be essential for Epstein-Barr virus-driven B-cell transformation, is overexpressed in several histologic subtypes of B-cell non-Hodgkin's lymphomas (NHL) and is required for the driver activity of oncogenes such as MYC and NOTCH. While these findings suggest that PRMT5 may act as a driver of lymphomagenesis, definitive experiments to address its driver activity have yet to be performed. To address this question, we developed a transgenic mouse model by immunoglobulin m heavy chain enhancer/promoter (Em)-driven PRMT5 over expression in the lymphoid compartment of FVB/N mice. Methods: Eµ-hPRMT5 transgenic mice were created by injecting a vector containing floxed human PRMT5 under the control of the Eµ enhancer/promoter into FVB/N pronuclei that were implanted into pseudo-pregnant FVB/N mice. We obtained 5 founder lines demonstrating the presence of transgene construct by genotype PCR analysis of tail snip DNA. Founder mice were crossed with wild type FVB/N mice to obtain a F1 generation. Mice were followed clinically in standard pathogen-free housing until exhibiting phenotypic features at which time necropsy was performed. Immunophenotypic analysis was performed by flow cytometry, clonality by T cell receptor (TCR) Vb PCR, and pathology by hematoxylin-eosin staining and tissue micro-arrays developed for immunohistochemical staining (IHCS). Statistical significance was determined using a two-tail t-test and survival analysis conducted using Kaplan Meier curves. Results: F1 generation Eµ-hPRMT5 mice significantly overexpressed PRMT5 mRNA in unpurified splenocytes or bone marrow relative to non-transgenic mice (p-value < 0.001). Sorting B (CD19), NK (NK1.1) and T-cell (CD3) mononuclear subsets from splenocytes collected from Eµ-hPRMT5 mice (n=3/group) revealed PRMT5 mRNA to be overexpressed 37-fold (p-value <0.01), 7-fold (p-value <0.01) and 6-fold (p-value <0.05), respectively compared to WT FVB/N mice. All 5 founder lines were found to develop aggressive lymphomas at a statistically significant higher incidence compared to wild type (WT) FVB/N mice (range 10.7-34.6% lymphomagenesis). Gross anatomical characterization of Lymphoma bearing mice demonstrated focal lymphoid tumors, lymphadenopathy, organomegaly (liver, spleen, kidney), and malignant atypical lymphocytosis. Flow cytometric and IHCS studies showed features consistent with immature pre B and T lymphoblastic lymphomas (LL). Pre B LLs were characterized by high surface IgM, TdT and CD19 expression as analyzed by flow cytometry. Pre T LL demonstrated cytoplasmic CD3, TdT, and CD43 expression. We successfully developed a T LL cell line (Tg813) from a pre T-LL tumor isolated from a thymic tumor. Tg813 was clonal (Vb-17), demonstrated complex cytogenetic features, and over-expressed PRMT5, CYCLIN D1, CYCLIN D3, C-MYC transcript and protein, and the PRMT5 histone mark, symmetric (Me2)-H4R3. Inhibition of PRMT5 with a small molecule inhibitor, shRNA or genetic deletion using CRISPR/CAS9 PRMT5-specific gRNA (targeting exon 2) led to reduced proliferation, apoptosis and loss of CYCLIN D1 and C-MYC expression in Tg813. Engraftment of the Tg813 LL into both SCID and immunocompetent FVB/N mice led to disseminated lymphomas 21 days post-engraftment. In vivo induced expression of PRMT5 gRNA in CAS9+ Tg813 tumors is currently underway. Conclusions:The spontaneous lymphomagenesis observed in the Eµ-hPRMT5 transgenic mouse model supports the hypothesis that PRMT5 over-expression can provide sufficient driver activity for this disease. We describe a novel in vivo and in vitro model of PRMT5-driven LL that provides a useful platform for studying the biologic role of this epigenetic modifier in cancer and for development of PRMT5 targeted therapeutic approaches for lymphoma. Disclosures Baiocchi: Essanex: Research Funding.

scholarly journals Protein Kinase B Regulates T Lymphocyte Survival, Nuclear Factor κb Activation, and Bcl-XL Levels in Vivo

2000 ◽  
Vol 191 (10) ◽  
pp. 1721-1734 ◽  
Author(s):  
Russell G. Jones ◽  
Michael Parsons ◽  
Madeleine Bonnard ◽  
Vera S.F. Chan ◽  
Wen-Chen Yeh ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Protein Kinase B ◽  
Active Form ◽  
Nuclear Factor ◽  
Clonal Deletion ◽  
Lymphocyte Survival

The serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4+CD8+ double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I–restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen–specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-XL. In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-κB activation via accelerated degradation of the NF-κB inhibitory protein IκBα. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-XL, and NF-κB) in vivo in T lymphocytes.

Cytotoxic T lymphocytes and viral evolution in primary HIV-1 infection*

1999 ◽  
Vol 97 (6) ◽  
pp. 707-718 ◽  
Author(s):  
David A. PRICE ◽  
Chris A. O'CALLAGHAN ◽  
Joseph A. WHELAN ◽  
Philippa J. EASTERBROOK ◽  
Rodney E. PHILLIPS
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Viral Evolution ◽  
Case Series ◽  
Effector Cells ◽  
Lymphocyte Responses ◽  
Hiv 1

Efforts to develop immune-based therapies for HIV infection have been impeded by incomplete definition of the immunological correlates of protection. Despite many precedents demonstrating that CD8+ cytotoxic T lymphocytes are key mediators of protective anti-viral immunity in non-human animal models, direct evidence that these effector cells control viral replication in HIV-1 infection has remained elusive. The first part of this paper describes a detailed immunological and genetic study founded on evolutionary considerations. Following infection with HIV-1, virus variants which escaped recognition by autologous cytotoxic T lymphocytes were shown to possess a selection advantage within the host environment. Cytotoxic T lymphocytes therefore exert anti-viral pressure in vivo. This observation provides compelling evidence that cytotoxic T lymphocytes comprise a significant element of anti-retroviral immunity. Subsequently, the quantification of peripheral cytotoxic T lymphocyte frequencies utilizing peptide–(human leucocyte antigen class I) tetrameric complexes is described. Five patients with qualitatively similar immunodominant cytotoxic T lymphocyte responses during symptomatic primary HIV-1 infection were studied longitudinally. Expansions of virus-specific CD8+ lymphocytes comprising up to 2% of the total CD8+ T cell population were observed in the acute phase of infection. Antigenic load was identified as an important determinant of circulating HIV-1-specific CD8+ lymphocyte levels; however, significant numbers of such cells were also found to persist following prolonged therapeutic suppression of plasma viraemia. In addition, an analysis of antigenic sequence variation with time in this case series suggests that the early administration of combination anti-retroviral therapy may limit HIV-1 mutational escape from host cytolytic specificities. The implications of these preliminary data are discussed. The data presented suggest that vaccination protocols should aim to elicit vigorous cytotoxic T lymphocyte responses to HIV-1. Attempts to stimulate polyvalent responses to mutationally intolerant epitopes are likely to be most effective. Optimal management of HIV-1 infection requires an understanding of dynamic host–virus interactions, and may involve strategies designed to enhance cytotoxic T lymphocyte activity following periods of anti-retroviral drug therapy.

scholarly journals Impaired Brain Mitochondrial Bioenergetics in the Ts65Dn Mouse Model of Down Syndrome Is Restored by Neonatal Treatment with the Polyphenol 7,8-Dihydroxyflavone

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 62
Author(s):  
Daniela Valenti ◽  
Fiorenza Stagni ◽  
Marco Emili ◽  
Sandra Guidi ◽  
Renata Bartesaghi ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Critical Role ◽  
Hippocampal Neurogenesis ◽  
In Vivo Studies ◽  
Mitochondrial Bioenergetics ◽  
Ts65dn Mouse ◽  
Atp Production

Down syndrome (DS), a major genetic cause of intellectual disability, is characterized by numerous neurodevelopmental defects. Previous in vitro studies highlighted a relationship between bioenergetic dysfunction and reduced neurogenesis in progenitor cells from the Ts65Dn mouse model of DS, suggesting a critical role of mitochondrial dysfunction in neurodevelopmental alterations in DS. Recent in vivo studies in Ts65Dn mice showed that neonatal supplementation (Days P3–P15) with the polyphenol 7,8-dihydroxyflavone (7,8-DHF) fully restored hippocampal neurogenesis. The current study was aimed to establish whether brain mitochondrial bioenergetic defects are already present in Ts65Dn pups and whether early treatment with 7,8-DHF positively impacts on mitochondrial function. In the brain and cerebellum of P3 and P15 Ts65Dn pups we found a strong impairment in the oxidative phosphorylation apparatus, resulting in a deficit in mitochondrial ATP production and ATP content. Administration of 7,8-DHF (dose: 5 mg/kg/day) during Days P3–P15 fully restored bioenergetic dysfunction in Ts65Dn mice, reduced the levels of oxygen radicals and reinstated the hippocampal levels of PGC-1α. No pharmacotherapy is available for DS. From current findings, 7,8-DHF emerges as a treatment with a good translational potential for improving mitochondrial bioenergetics and, thus, mitochondria-linked neurodevelopmental alterations in DS.

In Vivo Requirements for the Immune Recognition of L1210 Leukemia Cells by Allogeneic T-Lymphocytes

1983 ◽  
Vol 69 (5) ◽  
pp. 403-408
Author(s):  
Guido Forni ◽  
Luisa Lanfrancone ◽  
Mirella Giovarelli
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Immune Recognition ◽  
L1210 Leukemia ◽  
Simultaneous Presence ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens

The resistance of normal BALB/c mice (H-2d) against the L1210 Ha leukemia of DBA/2 mouse (H-2d) origin is due to the T-lymphocyte-dependent reaction towards DBA/2 multiple minor histocompatibility antigens (Mhas). These Mhas are displayed by the leukemic cells, though in a poorly immunogenic manner. The simultaneous presence of mitomycin C-inactivated DBA/2 leukocytes induces a significantly stronger T-lymphocyte-dependent reaction. This efficient presentation of target Mhas is restricted to Ia+ leukocytes. Their presence significantly increases BALB/c resistance, even when they are injected 3 days after the L1210 Ha challenge.

scholarly journals Synthesis and characterization of an antihuman T-lymphocyte saporin immunotoxin (OKT1-SAP) with in vivo stability into nonhuman primates

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 756-765 ◽  
Author(s):  
S Siena ◽  
DA Lappi ◽  
M Bregni ◽  
A Formosa ◽  
S Villa ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Dna Synthesis ◽  
T Lymphocyte ◽  
Whole Blood ◽  
Solid Phase ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Cells ◽  
Blood Components

Abstract The authors conjugated, by a disulphide bond, the antihuman T- lymphocyte (CD5) monoclonal antibody (MoAb) OKT1 to the saporin-6 (SAP) ribosome-inactivating protein of the plant Saponaria officinalis. The resulting OKT1-SAP immunotoxin bound to CD5-expressing target cells and under standard culture conditions specifically suppressed mitogen- induced-T-lymphocyte DNA and protein synthesis in a dose-related manner. T-lymphocyte killing was achieved by five-minute exposure of the target cells to OKT1-SAP. The concentration inhibiting 50% (IC50) of T-lymphocyte DNA synthesis was 0.32 nmol/L. The potency of OKT1-SAP was moderately enhanced by amantadine (IC50 0.08 nmol/L) but not by ammonium chloride or chloroquine. Whole blood components did not interfere with the efficacy of OKT1-SAP, as in vitro treatment of fresh whole blood resulted in effective elimination of clonable peripheral blood T-lymphocytes assessed by a limiting dilution assay. Because these characteristics of T-lymphocyte killing by OKT1-SAP (ie, rapidity of action, potency also without potentiators) and lack of inhibition by whole blood components may be relevant for the use of an immunotoxin as a therapeutic agent in humans, the authors evaluated the stability in vivo and the circulatory clearance of OKT1-SAP in cynomolgus monkeys. Following a single intravenous (IV) injection of nontoxic dosages (0.16 to 1.3 mg/kg), an initial rapid decline (t1/2 alpha = 1.0 to 4.1 hours) was followed by a long-lasting slower decrease (t1/2 beta = 11.6 to 20.6 hours) of OKT1-SAP plasma concentrations as detected by double- antibody solid phase enzyme-linked immunosorbent assay (ELISA) assay. Not only did OKT1-SAP remain intact immunologically but it also retained its biological activity, as measured by the ability of plasma samples from monkeys given immunotoxin to inhibit DNA synthesis in human T-lymphocytes. Taken together the findings presented in this article indicate the feasibility of using OKT1-SAP as a therapeutic tool and provide information that will facilitate the rational use of immunotoxins as a treatment modality in humans.

Gangliosides and glycophorin inhibit T-lymphocyte activation

1990 ◽  
Vol 68 (4) ◽  
pp. 735-744 ◽  
Author(s):  
Frances J. Sharom ◽  
Anita L. H. Chiu ◽  
T. Elaine Ross
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Interleukin 2 ◽  
Lymphocyte Activation ◽  
Bovine Brain ◽  
Inhibition Of Proliferation ◽  
Mechanism Of Inhibition ◽  
Dependent Cell ◽  
Brain Gangliosides

Increased levels of gangliosides in the serum have been linked to tumour-induced immunosuppression in vivo. Both bovine brain gangliosides and human erythrocyte glycophorin were potent inhibitors of concanavalin A, periodate, and phorbol ester – ionomycin induced activation of murine T-lymphocytes. Structurally complex gangliosides were more inhibitory, while simpler glycolipids caused less inhibition. Lymphocytes exposed to these molecules for up to 24 h could still proliferate after washing. Substantial inhibition was observed only when gangliosides and glycophorin were present during the first 18 h of activation. Studies using Quin-2 showed that gangliosides did not block the initial rapid rise in cytoplasmic Ca2+ following mitogen stimulation. Interleukin-2 (IL-2) production by ganglioside- and glycophorin-treated lymphocytes was unchanged. After treatment with gangliosides for 24 h, lymphocytes proliferated normally in response to added IL-2. These results suggest that the first round of signal transduction in response to mitogen was unaffected by gangliosides. Addition of gangliosides to activated lymphocytes in the presence of IL-2 resulted in complete inhibition of proliferation. Immunosuppression by gangliosides and glycophorin thus appears to occur at the IL-2-dependent stage of proliferation and may be partially due to IL-2 binding to these molecules. However, high levels of IL-2 failed to reverse inhibition and IL-2-dependent cell lines were much less sensitive to ganglioside inhibition than T-lymphocytes, suggesting that more than one mechanism of inhibition likely exists.Key words: gangliosides, glycophorin, T-lymphocyte, interleukin-2, interleukin-2 receptor.

scholarly journals Distinct Chemokine Triggers and In Vivo Migratory Paths of Fluorescein Dye-Labeled T Lymphocytes in Acutely Simian Immunodeficiency Virus SIVmac251-Infected and Uninfected Macaques

2005 ◽  
Vol 79 (21) ◽  
pp. 13759-13768 ◽  
Author(s):  
Candice C. Clay ◽  
Denise S. Rodrigues ◽  
Danielle J. Harvey ◽  
Christian M. Leutenegger ◽  
Ursula Esser
Keyword(s):  
Small Intestine ◽  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Chemokine Receptors ◽  
Lymphocyte Trafficking ◽  
Lymphocyte Depletion ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT To define the possible impact of T-lymphocyte trafficking parameters on simian immunodeficiency virus (SIV) pathogenesis, we examined migratory profiles of carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled T lymphocytes in acutely SIVmac251-infected and uninfected macaques within 48 h after autologous transfer. Despite significant upregulation of homeostatic chemokine CCL19/macrophage inflammatory protein 3β and proinflammatory chemokine CXCL9/monokine induced by gamma interferon in secondary lymphoid tissue in SIV infection, no differences in CFSE+ T-lymphocyte frequencies or cell compartmentalization in lymph nodes were identified between animal groups. By contrast, a higher frequency of CFSE+ T lymphocytes in the small intestine was detected in acute SIV infection. This result correlated with increased numbers of gut CD4 T lymphocytes expressing chemokine receptors CCR9, CCR7, and CXCR3 and high levels of their respective chemokine ligands in the small intestine. The changes in trafficking parameters in SIV-infected macaques occurred concomitantly with acute gut CD4 T-lymphocyte depletion. Here, we present the first in vivo T-lymphocyte trafficking study in SIV infection and a novel approach to delineate T-lymphocyte recruitment into tissues in the nonhuman primate animal model for AIDS. Such studies are likely to provide unique insights into T-lymphocyte sequestration in distinct tissue compartments and possible mechanisms of CD4 T-lymphocyte depletion and immune dysfunction in simian AIDS.

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