Mucosal and Peripheral Lin
 −
 HLA-DR
 +
 CD11c/123
 −
 CD13
 +
 CD14
 −
 Mononuclear Cells Are Preferentially Infected during Acute Simian Immunodeficiency Virus Infection

Moore, Andrew; Bixler, Sandra L.; Lewis, Mark G.; Verthelyi, Daniela; Mattapallil, Joseph J.

doi:10.1128/jvi.06372-11

Cited by 25 publications

(21 citation statements)

References 60 publications

(83 reference statements)

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“…50 Animal models show that HLA-DR + -activated T cells and macrophages are productively infected during the early stage of SIV/HIV infection and constitute one of the main targets for the virus. 51,52 In our study, DMPA increased CD3 …”

Section: Figsupporting

confidence: 58%

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Chandra

Thurman

Anderson

et al. 2013

AIDS Research and Human Retroviruses

102

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The relationship between exogenous contraceptive hormones and permissiveness of the female genital tract to human immunodeficiency virus type 1 (HIV-1) is the subject of renewed debate. To better characterize the effect of depot medroxyprogesterone acetate (DMPA) on HIV-1 cellular targets and epithelial integrity in the vagina, we compared leukocyte populations, markers of activation and proliferation, and the density of intercellular junctional proteins in the vaginal epithelium of women during the follicular and luteal phases of the menstrual cycle and approximately 12 weeks after receiving a DMPA injection. This prospective cohort study involved 15 healthy women. Vaginal biopsies were obtained in the follicular and luteal phases of the menstrual cycle, and approximately 12 weeks following a 150-mg intramuscular injection of DMPA. Leukocyte populations, activation phenotype, and epithelial tight junction and adherens proteins were evaluated by immunohistochemistry. After receiving DMPA, the numbers of CD45, CD3, CD8, CD68, HLA-DR, and CCR5 bearing immune cells were significantly ( p < 0.05) increased in vaginal tissues, compared to the follicular and/or luteal phases of untreated cycles. There were no significant differences in immune cell populations between the follicular and luteal phases of the control cycle. There were also no statistically significant differences in epithelial thickness and density of epithelial tight junction and adherens proteins among the follicular, luteal, and post-DMPA treatment sampling points. In this pilot study, vaginal immune cell populations were significantly altered by exogenous progesterone, resulting in increased numbers of T cells, macrophages, and HLA-DR-and CCR5-positive cells.

show abstract

Section: Figsupporting

confidence: 58%

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Chandra

Thurman

Anderson

et al. 2013

AIDS Research and Human Retroviruses

102

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“…Despite an extensive search in diverse lymphoid tissues using in situ hybridization and multilabel confocal microscopy, only CD3 ϩ T cells and not CD68 ϩ macrophages were infected throughout the course of infection. These findings are in contrast to SIVmac239, where despite the limited ability of this virus to infect macrophages in vitro (23,77,78), abundant infection of cells in the monocyte/macrophage lineage is typically seen (58,59,79). These findings could not be explained by differences in CD4 tropism or coreceptor utilization, since the ⌬GY Env showed no changes in CD4 or CCR5 utilization in cell-cell fusion assays or as an infectious virus (J. Hoxie, unpublished observations).…”

Section: Discussionmentioning

confidence: 83%

Loss of a Tyrosine-Dependent Trafficking Motif in the Simian Immunodeficiency Virus Envelope Cytoplasmic Tail Spares Mucosal CD4 Cells but Does Not Prevent Disease Progression

Breed

Jordan

Aye

et al. 2013

J Virol

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A hallmark of pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections is the rapid and near-complete depletion of mucosal CD4؉ T lymphocytes from the gastrointestinal tract. Loss of these cells and disruption of epithelial barrier function are associated with microbial translocation, which has been proposed to drive chronic systemic immune activation and disease progression. Here, we evaluate in rhesus macaques a novel attenuated variant of pathogenic SIVmac239, termed ⌬GY, which contains a deletion of a Tyr and a proximal Gly from a highly conserved YxxØ trafficking motif in the envelope cytoplasmic tail. Compared to SIVmac239, ⌬GY established a comparable acute peak of viremia but only transiently infected lamina propria and caused little or no acute depletion of mucosal CD4؉ T cells and no detectable microbial translocation. Nonetheless, these animals developed T-cell activation and declining peripheral blood CD4؉ T cells and ultimately progressed with clinical or pathological features of AIDS. ⌬GY-infected animals also showed no infection of macrophages or central nervous system tissues even in late-stage disease. Although the ⌬GY mutation persisted, novel mutations evolved, including the formation of new YxxØ motifs in two of four animals. These findings indicate that disruption of this trafficking motif by the ⌬GY mutation leads to a striking alteration in anatomic distribution of virus with sparing of lamina propria and a lack of microbial translocation. Because these animals exhibited wild-type levels of acute viremia and immune activation, our findings indicate that these pathological events are dissociable and that immune activation unrelated to gut damage can be sufficient for the development of AIDS.

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“…Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation and mesenteric lymph nodes were processed as previously described [16], [17], [18], [19], [20], [21]. Samples collected from the 7 healthy animals were used in the various experiments.…”

Section: Methodsmentioning

confidence: 99%

Rhesus Macaque Lymph Node PD-1hiCD4+ T Cells Express High Levels of CXCR5 and IL-21 and Display a CCR7loICOS+Bcl6+ T-Follicular Helper (Tfh) Cell Phenotype

et al. 2013

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CD4 T follicular helper (Tfh) cells play a unique and essential role in the generation of B cell responses in the lymph node microenvironment. Here we sought to determine if differential expression of PD-1 could be used to delineate Tfh cells in rhesus macaque lymph nodes (LN). CD3+CD4+ T cells were found to harbor a unique subset of cells that expressed the Program death-1 (PD-1) receptor at significantly high levels that were enriched in the LN compartment as compared to peripheral blood. The LN CD4+PD1hi T cells expressed a predominantly CD28+CD95+ central memory phenotype and were CCR7loICOShiBcl6hi. Additionally, CD4+PD1hi T cells preferentially expressed high levels of CXCR5 and IL-21 and significantly correlated with Bcl6+Ki-67+ IgG+ B cells. As Bcl6 is primarily expressed by proliferating B cells within active germinal centers, our results suggest that LN CD4+PD1hi T cells likely localize to active GC regions, a characteristic that is attributable to Tfh cells. Overall, our findings suggest that high levels of PD-1 expression on CD4+ T cells in LN of rhesus macaques can serve as a valuable marker to identify Tfh cells and has implications for studying the role of Tfh cells in Human immunodeficiency virus (HIV), Simian immunodeficiency virus (SIV) and other infectious diseases that use the rhesus macaque model.

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Mucosal and Peripheral Lin ⁻ HLA-DR ⁺ CD11c/123 ⁻ CD13 ⁺ CD14 ⁻ Mononuclear Cells Are Preferentially Infected during Acute Simian Immunodeficiency Virus Infection

Cited by 25 publications

References 60 publications

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Loss of a Tyrosine-Dependent Trafficking Motif in the Simian Immunodeficiency Virus Envelope Cytoplasmic Tail Spares Mucosal CD4 Cells but Does Not Prevent Disease Progression

Rhesus Macaque Lymph Node PD-1hiCD4+ T Cells Express High Levels of CXCR5 and IL-21 and Display a CCR7loICOS+Bcl6+ T-Follicular Helper (Tfh) Cell Phenotype

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Mucosal and Peripheral Lin − HLA-DR + CD11c/123 − CD13 + CD14 − Mononuclear Cells Are Preferentially Infected during Acute Simian Immunodeficiency Virus Infection

Cited by 25 publications

References 60 publications

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Depot Medroxyprogesterone Acetate Increases Immune Cell Numbers and Activation Markers in Human Vaginal Mucosal Tissues

Loss of a Tyrosine-Dependent Trafficking Motif in the Simian Immunodeficiency Virus Envelope Cytoplasmic Tail Spares Mucosal CD4 Cells but Does Not Prevent Disease Progression

Rhesus Macaque Lymph Node PD-1hiCD4+ T Cells Express High Levels of CXCR5 and IL-21 and Display a CCR7loICOS+Bcl6+ T-Follicular Helper (Tfh) Cell Phenotype

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Mucosal and Peripheral Lin ⁻ HLA-DR ⁺ CD11c/123 ⁻ CD13 ⁺ CD14 ⁻ Mononuclear Cells Are Preferentially Infected during Acute Simian Immunodeficiency Virus Infection