Activated cytotoxic lymphocytes in lymph nodes from human immunodeficiency virus (HIV) 1‐infected patients: a light and electronmicroscopic study

1997 ◽  
Vol 30 (1) ◽  
pp. 31-40 ◽  
Author(s):  
I. SUNILA ◽  
M. VACCAREZZA ◽  
G. PANTALEO ◽  
A.S. FAUCI ◽  
J.M. ORENSTEIN
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lymph Nodes ◽  
Cytotoxic Lymphocytes ◽  
Electronmicroscopic Study ◽  
Immunodeficiency Virus ◽  
Hiv 1

scholarly journals Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1.

1994 ◽  
Vol 179 (2) ◽  
pp. 513-522 ◽  
Author(s):  
T R Kollmann ◽  
M Pettoello-Mantovani ◽  
X Zhuang ◽  
A Kim ◽  
M Hachamovitch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Human T Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

A small animal model that could be infected with human immunodeficiency virus 1 (HIV-1) after peripheral inoculation would greatly facilitate the study of the pathophysiology of acute HIV-1 infection. The utility of SCID mice implanted with human fetal thymus and liver (SCID-hu mice) for studying peripheral HIV-1 infection in vivo has been hampered by the requirement for direct intraimplant injection of HIV-1 and the continued restriction of the resultant HIV-1 infection to the human thymus and liver (hu-thy/liv) implant. This may have been due to the very low numbers of human T cells present in the SCID-hu mouse peripheral lymphoid compartment. Since the degree of the peripheral reconstitution of SCID-hu mice with human T cells may be a function of the hu-thy/liv implant size, we increased the quantity of hu-thy/liv tissue implanted under the renal capsule and implanted hu-thy/liv tissue under the capsules of both kidneys. This resulted in SCID-hu mice in which significant numbers of human T cells were detected in the peripheral blood, spleens, and lymph nodes. After intraimplant injection of HIV-1 into these modified SCID-hu mice, significant HIV-1 infection was detected by quantitative coculture not only in the hu-thy/liv implant, but also in the spleen and peripheral blood. This indicated that HIV-1 infection can spread from the thymus to the peripheral lymphoid compartment. More importantly, a similar degree of infection of the hu-thy/liv implant and peripheral lymphoid compartment occurred after peripheral intraperitoneal inoculation with HIV-1. Active viral replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag RNA, and spliced tat/rev RNA in the hu-thy/liv implants, peripheral blood mononuclear cells (PBMC), spleens, and lymph nodes of these HIV-1-infected SCID-hu mice. As a first step in using our modified SCID-hu mouse model to investigate the pathophysiological consequences of HIV-1 infection, the effect of HIV-1 infection on the expression of human cytokines shown to enhance HIV-1 replication was examined. Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for human tumor necrosis factors alpha and beta, and interleukin 2 in their spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This suggested that HIV-1 infection in vivo can stimulate the expression of cytokine mRNA by human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Dendritic Cells Route Human Immunodeficiency Virus to Lymph Nodes after Vaginal or Intravenous Administration to Mice

1998 ◽  
Vol 72 (10) ◽  
pp. 7822-7829 ◽  
Author(s):  
Carole Masurier ◽  
Benoît Salomon ◽  
Nadia Guettari ◽  
Catherine Pioche ◽  
François Lachapelle ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Critical Role ◽  
Small Animal ◽  
Rna Sequences ◽  
Murine Bone Marrow ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We have developed a murine model to study the involvement of dendritic cells (DC) in human immunodeficiency virus (HIV) routing from an inoculation site to the lymph nodes (LN). Murine bone marrow-derived DC migrate to the draining LN within 24 h after subcutaneous injection. After incubation of these cells with heat-inactivated (Hi) HIV type 1 (HIV-1), HIV RNA sequences were detected in the draining LN only. Upon injection of DC pulsed with infectious HIV, the virus recovered in the draining LN was still able to productively infect human T cells. After a vaginal challenge with Hi HIV-1, the virus could be detected in the iliac and sacral draining LN at 24 h after injection. After an intravenous challenge, the virus could be detected in peripheral LN as soon as 30 min after injection. The specific depletion of a myeloid-related LN DC population, previously shown to take up blood macromolecules and to translocate them into the LN, prevented HIV transport to LN. Together, our data demonstrate the critical role of DC for HIV routing to LN after either a vaginal or an intravenous challenge, which does not require their infection. Therefore, despite the fact that the mouse is not infectable by HIV, this small animal model might be useful to test preventive strategies against HIV.

scholarly journals Early and Persistent Human Immunodeficiency Virus Type 1 (HIV‐1)–Specific T Helper Dysfunction in Blood and Lymph Nodes following Acute HIV‐1 Infection

1999 ◽  
Vol 180 (2) ◽  
pp. 278-284 ◽  
Author(s):  
Luwy K. Musey ◽  
John N. Krieger ◽  
James P. Hughes ◽  
Timothy W. Schacker ◽  
Lawrence Corey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lymph Nodes ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Helper ◽  
Immunodeficiency Virus ◽  
Acute Hiv ◽  
Hiv 1

scholarly journals Loss of CD4+ T Cells in Human Immunodeficiency Virus Type 1-Infected Chimpanzees Is Associated with Increased Lymphocyte Apoptosis

1998 ◽  
Vol 72 (6) ◽  
pp. 4623-4632 ◽  
Author(s):  
Ian C. Davis ◽  
Marc Girard ◽  
Patricia N. Fultz
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Human Immunodeficiency Virus Type ◽  
Cell Apoptosis ◽  
T Cell Apoptosis ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Supportive evidence that apoptosis contributes to loss of CD4+ lymphocytes in human immunodeficiency virus type 1 (HIV-1)-infected humans comes from an apparent lack of abnormal apoptosis in apathogenic lentivirus infections of nonhuman primates, including HIV-1 infection of chimpanzees. Two female chimpanzees were inoculated, one cervically and the other intravenously, with HIV-1 derived from the LAI/LAV-1b strain, which was isolated from a chimpanzee infected with the virus for 8 years. Within 6 weeks of infection, both recipient chimpanzees developed a progressive loss of CD4+ T cells which correlated with persistently high viral burdens and increased levels of CD4+ T-cell apoptosis both in vitro and in vivo. Lymph nodes from both animals also revealed evidence of immune hyperactivation. Intermediate levels of T-cell apoptosis in both peripheral blood and lymph nodes were seen in a third chimpanzee that had been infected with the LAI/LAV-1b strain for 9 years; this animal has maintained depressed CD4/CD8 T-cell ratios for the last 3 years. Similar analyses of cells from 4 uninfected animals and 10 other HIV-1-infected chimpanzees without loss of CD4+ cells revealed no difference in levels of apoptosis in these two control groups. These results demonstrate a correlation between immune hyperactivation, T-cell apoptosis, and chronic loss of CD4+ T cells in HIV-1-infected chimpanzees, providing additional evidence that apoptosis is an important factor in T-cell loss in AIDS. Furthermore, the results show that some HIV-1 strains are pathogenic for chimpanzees and that this species is not inherently resistant to HIV-1-induced disease.

scholarly journals Prime-Boost Immunization Schedules Based on Influenza Virus and Vaccinia Virus Vectors Potentiate Cellular Immune Responses against Human Immunodeficiency Virus Env Protein Systemically and in the Genitorectal Draining Lymph Nodes

2003 ◽  
Vol 77 (12) ◽  
pp. 7048-7057 ◽  
Author(s):  
M. Magdalena Gherardi ◽  
José Luis Nájera ◽  
Eva Pérez-Jiménez ◽  
Susana Guerra ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Influenza Virus ◽  
Immune Responses ◽  
Lymph Nodes ◽  
T Cell Response ◽  
Intranasal Route ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Hiv 1

ABSTRACT Vaccines that elicit systemic and mucosal immune responses should be the choice to control human immunodeficiency virus (HIV) infections. We have previously shown that prime-boost immunizations with influenza virus Env and vaccinia virus (VV) WR Env recombinants induced an enhanced systemic CD8+ T-cell response against HIV-1 Env antigen. In this report, we analyzed in BALB/c mice after priming with influenza virus Env the ability of two VV recombinants expressing HIV-1 Env B (VV WR Env and the highly attenuated modified VV Ankara [MVA] Env) to boost cellular immune responses in the spleen and in the lymph nodes draining the genital and rectal tracts. Groups of mice were primed by the intranasal route with 104 PFU of influenza virus Env and boosted 14 days later by the intraperitoneal or intranasal route with 107 PFU of MVA Env or VV WR Env, while the control group received two immunizations with influenza virus Env. We found that the combined immunization (Flu/VV) increased more than 60 times the number of gamma interferon-specific CD8+ T cells compared to the Flu/Flu scheme. Significantly, boosting with MVA Env by the intraperitoneal route induced a response 1.25 or 2.5 times (spleen or genital lymph nodes) higher with respect to that found after the boost with VV WR Env. Mice with an enhanced CD8+ T-cell response also had an increased Th1/Th2 ratio, evaluated by the cytokine pattern secreted following in vitro restimulation with gp160 protein and by the specific immunoglobulin G2a (IgG2a)/IgG1 ratio in serum. By the intranasal route recombinant WR Env booster gave a more efficient immune response (10 and 1.3 times in spleen and genital lymph nodes, respectively) than recombinant MVA Env. However, the scheme influenza virus Env/MVA Env increased four times the response in the spleen, giving a low but significant response in the genital lymph nodes compared with a single intranasal immunization with MVA Env. These results demonstrate that the combination Flu/MVA in prime-booster immunization regimens is an effective vaccination approach to generate cellular immune responses to HIV antigens at sites critical for protective responses.

Down-Regulation of Fas Expression in the Lymph Nodes of Patients Infected With Human Immunodeficiency Virus

2002 ◽  
Vol 126 (1) ◽  
pp. 28-32
Author(s):  
Liqiang Wang ◽  
Patrick A. Adegboyega
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Fas Ligand ◽  
Mononuclear Cells ◽  
Lymph Node Biopsy ◽  
Down Regulation ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Context.—The mechanism by which human immunodeficiency virus 1 (HIV-1) infection causes increased rates of apoptosis and gradual chronic depletion of CD4+ T lymphocytes in patients infected with HIV-1 is not known. Findings from in vitro culture studies and analysis of mononuclear cells in the peripheral blood of HIV-infected patients have led to the hypothesis that abnormal expression and/or interaction of Fas and Fas ligand (FasL) may play significant roles in the derangement of homeostasis of CD4+ lymphocytes in patients infected with HIV-1. Objective.—To determine the in situ expression of Fas and FasL in the lymph nodes of patients infected with HIV-1. Design.—Immunohistochemical expression of Fas and FasL was studied in the lymph node biopsy specimens from 20 patients infected with HIV-1. As controls, we also studied 120 lymph nodes from 28 HIV-1–seronegative patients with reactive lymphadenopathy. Results.—In the reactive lymph nodes of seronegative patients, expression of Fas was diffuse in the germinal centers and also in immunoblast-like cells in the T-cell regions. In the lymph nodes of patients infected with HIV, there was a consistent remarkable decrease in Fas expression in 12 of 20 patients and a total lack of Fas expression in the remaining 8 patients. Expression of FasL was comparable in both patient groups. Conclusions.—There is marked down-regulation of Fas in the lymph nodes of HIV-infected patients, a sharp contrast to what occurs in circulating mononuclear cells in the peripheral blood of these patients. These results indicate the need for further studies of this molecular event for possible therapeutic intervention based on reconstitution of Fas and/or FasL activity in the treatment of HIV infection.

scholarly journals Human Immunodeficiency Virus Type 1 Bound to B Cells: Relationship to Virus Replicating in CD4+ T Cells and Circulating in Plasma

2002 ◽  
Vol 76 (17) ◽  
pp. 8855-8863 ◽  
Author(s):  
Angela Malaspina ◽  
Susan Moir ◽  
David C. Nickle ◽  
Eileen T. Donoghue ◽  
Kisani M. Ogwaro ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Peripheral Blood ◽  
Lymphoid Tissues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) virions bind to B cells in the peripheral blood and lymph nodes through interactions between CD21 on B cells and complement-complexed virions. B-cell-bound virions have been shown to be highly infectious, suggesting a unique mode of HIV-1 dissemination by B cells circulating between peripheral blood and lymphoid tissues. In order to investigate the relationship between B-cell-bound HIV-1 and viruses found in CD4+ T cells and in plasma, we examined the genetic relationships of HIV-1 found in the blood and lymph nodes of chronically infected patients with heteroduplex mobility and tracking assays and DNA sequence analysis. In samples from 13 of 15 patients examined, HIV-1 variants in peripheral blood-derived B cells were closely related to virus in CD4+ T cells and more divergent from virus in plasma. In samples from five chronically viremic patients for whom analyses were extended to include lymph node-derived HIV-1 isolates, B-cell-associated HIV-1 and CD4+-T-cell-associated HIV-1 in the lymph nodes were equivalent in their divergence from virus in peripheral blood-derived B cells and generally more distantly related to virus in peripheral blood-derived CD4+ T cells. These results indicates virologic cross talk between B cells and CD4+ T cells within the microenvironment of lymphoid tissues and, to a lesser extent, between cells in lymph nodes and the peripheral blood. These findings also indicate that most of the virus in plasma originates from cells other than CD4+ T cells in the peripheral blood and lymph nodes.

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