Phenotypic characterization of CD8+ T cell populations in HIV disease and in anti-HIV immunity

Watret, Karen C.; Whitelaw, James; Froebel, K. S.; Bird, A. G.

doi:10.1111/j.1365-2249.1993.tb05953.x

Cited by 37 publications

(5 citation statements)

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“…In these children there was a rise in the proportion of HLA-DR* CD8 cells, and a decrease in the proportion of CD45RA* CD8 cells on the CTL* occasions, which is consistent with immune activation. However, there was no further expansion of S6F1 "^ CD8 cells, probably due to the very high levels already present in the blood (a phenomenon not seen to the same extent in adults [10]), giving little room for further expansion. On the CTL occasions, however, there was a lack of expansion of CD8 cells, and in particular a lack of increased expression of HLA-DR on CD8 cells, which was statistically significant.…”

Section: Discussionmentioning

confidence: 88%

“…We have previously reported that loss of CTL activity in adults was associated with a failure to expand of the CD45RO*, S6F1^ and HLA-DR' subpopulations of CD8 cells in bulk cultured effector cells [10]. In ihis study, to allow for the possibility that the CTL children may have CTL against target antigens not studied here, we limited the analysis of effector cell subpopulations to the five children who changed CTL activity during the study.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study in adults has suggested that it may be possible to indirectly Identify CTL by means of CDS subset markers in the cultured effector cells, in particular CD45RO, HLA-DR and S6F1 [10]. We and others have shown in HIVinfected children that CD8^ lymphocytes and specific subpopulations are present in abnormally high proportions [11.12].…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

Aldhous

Watret²,

Mok

et al. 1994

Clinical and Experimental Immunology

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SUMMARYHIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CDS lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any. between CTL activity and CDS subpopuiations. We have measured CTL activity against four HIV gene products (gag. tat. pal and en\) and expression of CD45RO, CD45RA. HLA-DR, CD29. S6F1, and CD57 surface markers on CDS cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HW-gag. -pot and -tat. and the other to HW-pot. All the HIV-infected and two uninfected children had abnormal proportions of CDS subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CDS subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CDS cells, an expansion of HLA-DR^ CD8 cells and a loss of CD45RA ' CDS cells.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

Aldhous

Watret²,

Mok

et al. 1994

Clinical and Experimental Immunology

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“…In fact, morphological changes resembling chronic inflammatory bowel disease can be induced by T cell activation in human fetal colon explants [26]. However, in vitro studies of eireulating T eells have shown that the activity of cytotoxic T cells is strongly dependent on the presence of CD4' T cells [27], therefore the specific activity of the cytotoxic T cells in the mucosa may be impaired due to intestinal CD4T cell depletion.…”

Section: Disclssionmentioning

confidence: 99%

Abnormalities in subset distribution, activation, and differentiation of T ceils isolated from large intestine biopsies in HIV infection

Schneider

Ullrich²,

Bergs³

et al. 1994

Clinical and Experimental Immunology

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Intestinal T cells have a unique state of activation and differentiation which might specifically affect or be affected by HIV infection. Lymphocyte subsets in the peripheral blood are well characterized, but our knowledge about intestinal lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes isolated from large intestine biopsies of AIDS patients and controls by three-colour cytofluorometry. In the large intestine of HIV-infected patients CD4 T cells were reduced and CD8 T cells were increased compared with controls. Most of the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxic phenotype. Activated and resting CD4 T cells were similarly reduced, the expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased, respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased expression of all these differentiation markers. Our findings demonstrate substantial alterations in subset distribution, activation, and differentiation of large intestine T cells, which may contribute to the secondary infections and malignancies commonly observed in the gut of AIDS patients.

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“…It has been shown that the frequency of CD8+ T cells expressing the S6F1 epitope is higher in HIV-1 infected individuals compared to uninfected controls [4,5]. The S6F1+ cell subset is not expanded in individuals with Epstein Barr Virus (EBV) infection [6], suggesting this epitope may play a unique role in the pathogenesis of HIV-1 infection and is not merely the result of expansion of this cell subset due to chronic viral infection.…”

Section: Introductionmentioning

confidence: 99%

A monoclonal antibody against lymphocyte function-associated antigen-1 decreases HIV-1 replication by inducing the secretion of an antiviral soluble factor

Rychert

Jones

McGrath

et al. 2013

Virol J

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BackgroundLymphocyte Function-Associated Antigen-1 (LFA-1) likely plays a role in the pathogenesis of against HIV-1 and is known to facilitate cell-to-cell transmission of the virus. A monoclonal antibody specific for LFA-1 (Cytolin®) was evaluated as a potential therapeutic in pilot studies performed in the mid-1990s. These uncontrolled human studies suggested that administration of this anti-LFA-1 antibody to HIV-1 infected individuals could provide a modest benefit by decreasing circulating HIV-1 RNA and increasing CD4+ T cell counts. At the time, it was proposed that when bound to cytolytic T cells, the antibody inhibited lysis of activated CD4+ T cells. Given the renewed interest in monoclonal antibody therapy for HIV-1 infected individuals, we investigated possible mechanisms of action of this antibody in vitro.MethodsTo assess whether this anti-LFA-1 antibody binds to HIV-1, a virus capture assay was performed. Binding of the antibody to cells was assessed using flow cytometry. Inhibition of HIV-1 replication was determined in culture by measuring the amount of p24 produced by ELISA. After co-culture of the antibody with peripheral blood mononuclear cells, supernatants were assayed for cytokines and chemokines using various immunoassays.ResultsOur experiments demonstrate that anti-LFA-1 antibody binds to CCR5 and CXCR4 utilizing strains of HIV-1. It also binds to CD8+ T cells and dendritic cells. When bound to virus prior to infection, there is no decrease in HIV-1 replication, suggesting it does not directly inhibit viral replication via virus binding. When bound to cells, it does not inhibit lysis of CD4+ T cells, as was originally hypothesized. Binding to cells does appear to induce the production of a soluble factor that inhibits HIV-1 replication. We determined that this soluble factor was not any of the cytokines or chemokines with known anti-HIV-1 activity. Further, the antibody does not appear to induce any common immune modulating cytokines or chemokines.ConclusionsThese results suggest that one possible mechanism of action of this anti-LFA-1 antibody is to inhibit HIV-1 replication via the production of a soluble antiviral factor that is induced upon binding to cells.

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Phenotypic characterization of CD8+ T cell populations in HIV disease and in anti-HIV immunity

Cited by 37 publications

References 39 publications

Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

Abnormalities in subset distribution, activation, and differentiation of T ceils isolated from large intestine biopsies in HIV infection

A monoclonal antibody against lymphocyte function-associated antigen-1 decreases HIV-1 replication by inducing the secretion of an antiviral soluble factor

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