scholarly journals Human immunodeficiency virus gag and pol-specific CD8 T cells in perinatal HIV infection

Cytometry ◽  
2001 ◽  
Vol 46 (5) ◽  
pp. 265-270 ◽  
Author(s):  
Thomas W. McCloskey ◽  
Viraga Haridas ◽  
Raj Pahwa ◽  
Savita Pahwa
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Perinatal Hiv ◽  
Immunodeficiency Virus

scholarly journals Selective anergy of V beta 8+ T cells in human immunodeficiency virus-infected individuals.

1994 ◽  
Vol 179 (2) ◽  
pp. 413-424 ◽  
Author(s):  
G Dadaglio ◽  
S Garcia ◽  
L Montagnier ◽  
M L Gougeon
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Clinical Status ◽  
Interleukin 2 ◽  
Cell Subset ◽  
T Cell Subset ◽  
Immunodeficiency Virus

We have analyzed the V beta usage by CD4+ and CD8+ T cells from human immunodeficiency virus (HIV)-infected individuals in response to an in vitro stimulation with the superantigenic erythrogenic toxin A (ETA) of Streptococcus pyogenes. ETA amplifies specifically CD4+ and CD8+ T cells from control donors expressing the V beta 8 and the V beta 12 elements. When peripheral T cells from asymptomatic HIV-infected individuals were stimulated with ETA, there was a complete lack of activation of the V beta 8+ T cell subset, whereas the V beta 12+ T cell subset responded normally to the superantigen. This V beta-specific anergy, which was also observed in response to staphylococcal enterotoxin E (SEE), affected both CD4+ and CD8+ T cells and represented an intrinsic functional defect rather than a specific lack of response to bacterial superantigens since it was also observed after a stimulation with V beta 8 monoclonal antibodies. The V beta 8 anergic T cells did not express interleukin 2 receptors (IL-2Rs) and failed to proliferate in response to exogenous IL-2 or IL-4, suggesting that this anergy was not a reversible process, at least by the use of these cytokines. The unresponsiveness of the V beta 8 T cell subset is frequent since it was found in 56% of the patients studied, and comparison of the clinical status of responder vs. anergic patients indicated that the only known common factor between them was HIV infection. In addition, it is noteworthy that the anergy of the V beta 8 subset may be a very early phenomenon since it was found in a patient at Centers for Disease Control stage I of the disease. These data provide evidence that a dominant superantigen may be involved in the course of HIV infection and that the contribution of HIV has to be considered.

scholarly journals Decreased CXCR3+ CD8 T Cells in Advanced Human Immunodeficiency Virus Infection Suggest that a Homing Defect Contributes to Cytotoxic T-Lymphocyte Dysfunction

2007 ◽  
Vol 81 (16) ◽  
pp. 8439-8450 ◽  
Author(s):  
Diana M. Brainard ◽  
Andrew M. Tager ◽  
Joseph Misdraji ◽  
Nicole Frahm ◽  
Mathias Lichterfeld ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Lymphoid Tissue ◽  
Chronic Infection ◽  
Advanced Disease ◽  
Receptor Expression ◽  
Effector Memory ◽  
Immunodeficiency Virus

ABSTRACT To exert their cytotoxic function, cytotoxic T-lymphocytes (CTL) must be recruited into infected lymphoid tissue where the majority of human immunodeficiency virus (HIV) replication occurs. Normally, effector T cells exit lymph nodes (LNs) and home to peripheral sites of infection. How HIV-specific CTL migrate into lymphoid tissue from which they are normally excluded is unknown. We investigated which chemokines and receptors mediate this reverse homing and whether impairment of this homing could contribute to CTL dysfunction as HIV infection progresses. Analysis of CTL chemokine receptor expression in the blood and LNs of untreated HIV-infected individuals with stable, chronic infection or advanced disease demonstrated that LNs were enriched for CXCR3+ CD8 T cells in all subjects, suggesting a key role for this receptor in CTL homing to infected lymphoid tissue. Compared to subjects with chronic infection, however, subjects with advanced disease had fewer CXCR3+ CD8 T cells in blood and LNs. CXCR3 expression on bulk and HIV-specific CD8 T cells correlated positively with CD4 count and negatively with viral load. In advanced infection, there was an accumulation of HIV-specific CD8 T cells at the effector memory stage; however, decreased numbers of CXCR3+ CD8 T cells were seen across all maturation subsets. Plasma CXCL9 and CXCL10 were elevated in both infected groups in comparison to the levels in uninfected controls, whereas lower mRNA levels of CXCR3 ligands and CD8 in LNs were seen in advanced infection. These data suggest that both CXCR3+ CD8 T cells and LN CXCR3 ligands decrease as HIV infection progresses, resulting in reduced homing of CTL into LNs and contributing to immune dysfunction.

scholarly journals CD8+ T lymphocytes provide helper activity for IgE synthesis in human immunodeficiency virus-infected patients with hyper-IgE.

1995 ◽  
Vol 181 (1) ◽  
pp. 423-428 ◽  
Author(s):  
R Paganelli ◽  
E Scala ◽  
I J Ansotegui ◽  
C M Ausiello ◽  
E Halapi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cd4 Cells ◽  
In Vitro Synthesis ◽  
Immunodeficiency Virus ◽  
Ige Synthesis

Increased levels of serum IgE and eosinophilia have been described in human immunodeficiency virus (HIV) infection, almost exclusively in patients with CD4+ cell count < 200 cells/microliters. IgE production is regulated by CD4+ T helper type 2 (Th-2) lymphocytes, producing interleukin 4 (IL-4) and expressing a ligand for the B cell-specific CD40 molecule (CD40 ligand [L]). A shift to a Th-2-like pattern of cytokine secretion has been postulated to be associated with progression toward acquired immunodeficiency syndrome (AIDS). We studied three AIDS patients with very high levels of IgE and almost complete depletion of CD4+ lymphocytes, suggesting that IgE synthesis could not be driven by CD4+ cells. IgE in vitro synthesis by cells from such patients was, however, inhibited by anti-IL-4. We show that both CD8+ T cell lines and the majority of CD8+ T cells clones derived from these patients produce IL-4, IL-5, and IL-6 in half of the cases together with interferon gamma (IFN-gamma). 44% of CD8+ T cell clones expressed a CD40L, and the supernatants of the clones were capable of inducing IgE synthesis by normal B cells costimulated with anti-CD40. CD8+ T cells in these patients therefore functionally mimic Th-2 type cells and may account for hyper-IgE and eosinophilia in the absence of CD4+ cells. The presence of such CD8+ cells may also provide a source of IL-4 directing the development of predominant Th-2 responses in HIV infection.

Perinatal Human Immunodeficiency Virus (HIV) Testing

PEDIATRICS ◽  
1992 ◽  
Vol 89 (4) ◽  
pp. 791-794
Author(s):  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Vertical Transmission ◽  
Task Force ◽  
Perinatal Transmission ◽  
Pediatric Hiv ◽  
Number Of Children ◽  
Perinatal Hiv ◽  
Seroprevalence Data ◽  
Immunodeficiency Virus

PERINATAL INFECTIONS The primary route of human immunodeficiency virus (HIV) infection in infants is vertical transmission from HIV-infected mothers. This is of particular concern as the number of infected women and the number of children infected by perinatal transmission continue to increase rapidly. The number of perinatally acquired acquired immunodeficiency syndrome (AIDS) cases increased 17% in 1989 and 21% in 1990. Similarly, the number of heterosexually acquired AIDS cases increased 27% in 1989 and 40% in 1990. There is evidence that vertical transmission of HIV can occur in utero (congenital/transplacental, similar to rubella),1,2 in the postpartum period (breast-feeding), and perhaps in the intrapartum period (similar to hepatitis B).3 The relative frequency and efficiency of transmission during each of these periods remains uncertain. The best estimates of vertical transmission from an HIV-seropositive mother to the fetus range from 12.9% to 39%4-6 Although the risk of transmission appears to be increased in women who are symptomatic, this point is still unclear.5 Preliminary information suggests that the presence of high levels of high-affinity/avidity antibodies to specific epitopes of the gp 120 of HIV may be protective and may decrease or prevent vertical transmission,7-10 although others have not been able to confirm this finding.11 More detailed information on perinatal HIV infection,12 and infection control13 in pediatric HIV infection is available in previously published statements from the AAP Task Force on Pediatric AIDS. SEROPREVALENCE Anonymous seroprevalence data from newborn specimens are being collected in 44 states, Puerto Rico, and the District of Columbia. In some states, seroprevalence data are available by metropolitan area and/or by hospital of birth.

scholarly journals Interleukin 7 Increases Human Immunodeficiency Virus Type 1 LAI-Mediated Fas-Induced T-Cell Death

2005 ◽  
Vol 79 (5) ◽  
pp. 3195-3199 ◽  
Author(s):  
Jean-Daniel Lelièvre ◽  
Frédéric Petit ◽  
Damien Arnoult ◽  
Jean-Claude Ameisen ◽  
Jérôme Estaquier
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Infection ◽  
Interleukin 7 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Fas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1LAI) primes CD8+ T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8+ T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8+ T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4+ and CD8+ T-cell death induced by HIV-1LAI. Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1LAI and IL-7 is one of the mechanisms involved in progression to AIDS.

scholarly journals Potent activity of 2'-beta-fluoro-2',3'-dideoxyadenosine against human immunodeficiency virus type 1 infection in hu-PBL-SCID mice.

1996 ◽  
Vol 40 (10) ◽  
pp. 2369-2374 ◽  
Author(s):  
K Ruxrungtham ◽  
E Boone ◽  
H Ford ◽  
J S Driscoll ◽  
R T Davey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Infection ◽  
Infection Rate ◽  
Cd4 T Cells ◽  
Scid Mice ◽  
Immunodeficiency Virus ◽  
Anti Hiv

A new antiretroviral agent, 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA), is an acid-stable compound whose triphosphate form is a potent reverse transcriptase inhibitor with in vitro anti-human immunodeficiency virus (HIV) activity and a favorable pharmacokinetic profile. Severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) provide a useful small-animal model for HIV research. In the present study we utilized this experimental system for the in vivo evaluation of the anti-HIV activity of this new compound when administered prior to infection. Initial studies revealed that, following a challenge with 50 100% tissue culture infective doses of HIV type 1 lymphadenopathy-associated virus, 39 of 42 (93%) control mice developed HIV infection, as evidenced by positive coculture or positive PCR. Administration of zidovudine decreased the infection rate to 5 of 16 (31%), while administration of FddA decreased the infection rate to 0 of 44 (0%). In follow-up controlled studies, the anti-HIV activity of FddA was confirmed, with 18 of 20 control mice showing evidence of HIV infection, compared with 4 of 20 FddA-treated mice. In addition to having direct anti-HIV effects, FddA was found to have a protective effect on human CD4+ T cells in the face of HIV infection. Mice treated with FddA were found to have a significantly higher percentage of CD4+ T cells than controls (10.3% +/- 3.4% versus 0.27% +/- 0.21%; P = 0.01). Thus, FddA, with its potent anti-HIV activity in vivo, high oral bioavailability, long intracellular half-life, and ability to preserve CD4+ cells in the presence of HIV, appears to be a promising agent for clinical investigation.

scholarly journals Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic Infection

2006 ◽  
Vol 80 (16) ◽  
pp. 8236-8247 ◽  
Author(s):  
Moraima Guadalupe ◽  
Sumathi Sankaran ◽  
Michael D. George ◽  
Elizabeth Reay ◽  
David Verhoeven ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Microarray Analysis ◽  
Dna Microarray ◽  
Peripheral Blood ◽  
Viral Suppression ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11α, αEβ7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

Detection and characterization of apoptotic peripheral blood lymphocytes in human immunodeficiency virus infection and cancer chemotherapy by a novel flow immunocytometric method

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1268-1277 ◽  
Author(s):  
M Carbonari ◽  
M Cibati ◽  
M Cherchi ◽  
D Sbarigia ◽  
AM Pesce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Infection ◽  
Peripheral Blood ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Cell Counts ◽  
Immunodeficiency Virus

We have developed a quantitative and sensitive flow cytometric method for the detection of human apoptotic lymphocytes that, unlike previously described assays, allows their identification in mixed populations of peripheral blood leukocytes as well as their immunophenotyping. Apoptotic lymphocytes are identified on the basis of peculiar light scatter changes, reflecting their smaller size and their modified nucleus/cytoplasm organization, and of the decreased expression of surface CD45 molecules. Based on these criteria, apoptotic lymphocytes generated by exposure to ionizing radiation can be easily distinguished from viable cells and from necrotic lymphocytes generated by treatment with antibody and complement. Using this assay, we reappraised the phenomenon of the in vitro apoptosis of lymphocytes from patients with human immunodeficiency virus (HIV) infection. Lymphocytes from HIV patients, unlike those from normal HIV-negative subjects, undergo apoptosis upon simple in vitro culture. We found that the percentages of lymphocytes undergoing apoptosis were significantly higher in patients with low CD4 cell counts (< 400/microL) than in patients at earlier stages (> 400 CD4 cells/microL). However, phenotypic analysis disclosed that apoptotic lymphocytes generated in these cultures were mostly CD8+ T cells and CD19+ B cells. Thus, in contrast to what has been previously suggested, the phenomenon of in vitro lymphocyte apoptosis might not be pathogenetically related to the depletion of CD4+ T cells in acquired immunodeficiency syndrome. Nevertheless, it might represent an useful marker of disease progression. Our assay allows the analysis of unfractionated peripheral blood leukocytes and thus the identification of apoptotic lymphocytes circulating in vivo. Apoptotic lymphocytes could indeed be detected in the circulation of a patient with cancer shortly after high-dose cytotoxic chemotherapy. By contrast, no apoptotic lymphocytes could be detected in vivo in patients with early or advanced HIV infection.

CD8 T-Cell Infiltration in Extravascular Tissues of Patients With Human Immunodeficiency Virus Infection. Interleukin-15 Upmodulates Costimulatory Pathways Involved in the Antigen-Presenting Cells–T-Cell Interaction

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1277-1286 ◽  
Author(s):  
Carlo Agostini ◽  
Renato Zambello ◽  
Monica Facco ◽  
Alessandra Perin ◽  
Francesco Piazza ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Binding Proteins ◽  
Antigen Presenting Cells ◽  
Cd8 T Cell ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Antigen Presenting

Interleukin (IL)-15 regulates the proliferative activity of the CD8+ T-cell pool in human immunodeficiency virus (HIV)-infected patients, thereby contributing to the maintenance of the CD8+ T-cell–mediated immune response against HIV in extravascular tissues, including the lung. However, the effects of IL-15 on antigen-presenting cells (APC) during HIV infection are still unclear. In this study, we evaluated whether IL-15 regulates the macrophage stimulatory pathways governing inflammatory events that take place in the lung of patients with HIV infection. As a first step we evaluated the in vitro effects of IL-15 on lung macrophages retrieved from the respiratory tract of eight normal subjects. Although macrophages from uninfected individuals expressed the IL-15 binding proteins (IL-15R and the common γc) at resting conditions, they did not express IL-15 messenger RNA (mRNA). However, a 24-hour stimulation with IL-15 induced the expression of interferon-γ (IFN-γ) and IL-15 itself, suggesting a role for this cytokine in the activation of the pulmonary macrophage pool during inflammation. As a confirmation of the role of IL-15 in this setting, at resting conditions, alveolar macrophages of patients with HIV infection and T-cell alveolitis expressed IL-15, IFN-γ, and IL-15 binding proteins; showed an upmodulation of costimulatory molecules, B7 and CD72, which are involved in the APC of macrophages; and behaved as effective accessory cells because they elicited a strong proliferation of T cells. The accessory effect was inhibited by pretreatment with anti-CD72, anti-B7 (CD80 and CD86), and anti–IL-15 monoclonal antibodies (MoAb). We then investigated the relationship between IL-15 and the expression of costimulatory molecules by macrophages. A 24-hour stimulation of IL-15R+/γc+ macrophages with IL-15 upregulated the expression of CD80 and CD86. The evidence that IL-15 upregulates the expression of coligands that favor the contact between T cells and APC, per se, triggers T-cell activation and proliferation and acts as a chemoattractant for T cells, suggests that IL-15 plays a key role in Tc1-mediated defense mechanisms taking place in extravascular tissues of patients with HIV disease.

scholarly journals Overexpression of a Novel Lymphocyte Population, Positive for an Intracellular CD14-Like Antigen, in Patients Positive for Human Immunodeficiency Virus Type 1

2004 ◽  
Vol 11 (6) ◽  
pp. 1040-1044 ◽  
Author(s):  
Dan Turner ◽  
Michael Hoffman ◽  
Israel Yust ◽  
Mordechai Fried ◽  
Margalit Bleiberg ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Population ◽  
Human Peripheral Blood ◽  
Soluble Form ◽  
Lymphocyte Population ◽  
Cellular Marker ◽  
Immunodeficiency Virus

ABSTRACT CD14, originally recognized as a lipopolysaccharide (LPS) receptor, has recently been implicated in the process of T-cell suppression and apoptosis. Its soluble form has been shown to bind, in vitro, to human T cells, a process that may carry a negative signal onto these cells. We recently described a novel lymphocyte population in human peripheral blood, a population that expresses an intracellular CD14-like antigen. This novel T-cell population, composed mainly of CD8 cells and of very few CD4 cells, was found to be greatly enhanced in asymptomatic, untreated human immunodeficiency virus (HIV)-positive individuals. In the present study, we further characterized this cell population and found that it differed from other CD8 subpopulations associated with HIV infection such as CD8/CD38. In addition, we followed HIV patients under conditions of highly active antiretroviral therapy (HAART) and observed two groups of patients: patients in whom the CD14-like positive-testing T cells returned to normal within 1 to 3 months, and patients in whom it did not, in spite of a significant plasma HIV-RNA viral load decrease. Thus, this new CD14-like positive-testing lymphocyte population may represent an interesting and important component of the cellular events associated with HIV infection. On the basis of its modulation following HAART, we speculate that it may be used, in the future, as a drug-monitoring cellular marker in antiretroviral treatment.

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