Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion

Klimas, Nancy G.; Patarca, Roberto; Walling, Jean; Garcia, R.; Mayer, V.; Moody, Dewey J.; Okarma, Thomas B.; Fletcher, Mary A

doi:10.1097/00002030-199408000-00006

Cited by 46 publications

(11 citation statements)

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“…after allogeneic BMT was accomplished by transfer of CMV-specific CD8+ T cell clones from the donor. Polyclonal CD8+ autologous T cell transfer following in vitro activation has also been attempted in patients with HIV-1 infection (11). Other studies have used genetically modified HIV-specific CD8+ T cells following allogeneic BMT (12).…”

mentioning

confidence: 99%

Large-Scale Production of CD4+ T Cells from HIV-1-Infected Donors After CD3/CD28 Costimulation*

Levine¹,

Cotte²,

Small³

et al. 1998

Journal of Hematotherapy

112

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We describe a procedure for large-scale enrichment, growth, and harvesting CD4+ T cells. This method may be effective for HIV-1 immunotherapy, as the mode of stimulation, with anti-CD3 plus anti-CD28 coated beads (CD3/CD28 beads) induces a potent antiviral effect. PBMC were obtained by density gradient centrifugation of an apheresis product. Monocytes/macrophages were removed by incubating PBMC with beads coated with IgG. The cells were then magnetically depleted of B cells and CD8+ cells with mouse anti-CD20 and anti-CD8 MAbs and sheep antimouse coated beads. The remaining cells were >80% CD4+ and were transferred to gas-permeable bags containing CD3/CD28 beads and cultured in a closed system. After 14 days, the cell number increased an average of 37-fold, and cells were nearly 100% CD4+. Viral load, assessed by DNA PCR for HIV-1 gag, decreased >10-fold during culture in the absence of antiretroviral agents. Removal of CD3/CD28 beads from the cell suspension was accomplished by passing cells plus beads (3-30 x 10(9) cells in 2-12 L) over a MaxSep magnetic separator using gravity-driven flow. The cells were then concentrated to 300 ml in an automated centrifuge. This process allows safe and efficient growth of large numbers of CD4+ T cells from HIV-1+ donors.

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mentioning

confidence: 99%

Large-Scale Production of CD4+ T Cells from HIV-1-Infected Donors After CD3/CD28 Costimulation*

Levine¹,

Cotte²,

Small³

et al. 1998

Journal of Hematotherapy

112

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“…Other adoptive transfer studies in animals and humans have evaluated single or multiple infusions using on the order of 10 7 to 10 11 lentivirus or melanoma-specific T-cells, with or without IL-2 administration (Brodie et al, 1999;Brodie et al, 2000;Dudley et al, 2002;Flynn et al, 2005;Ho et al, 1993;Klimas et al, 1994;Mitsuyasu et al, 2000;Pu et al, 1999;Villinger et al, 2002;Walker et al, 2000;Yee et al, 2002). Studies in mice indicate that immune CD4 + T cells are required for survival of infused virus-specific CD8+ T cells (Berger et al, 2000;Hunziker et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…In these patients, rhuIL-2 can augment immune responses and increase CD4+ T lymphocyte counts (Aladdin et al, 2000;Davey et al, 1997;Jacobson et al, 1996). Recombinant huIL-2 has also been administered to HIV-1-infected individuals to support adoptively transferred HIV-1-specific lymphocytes and CTL (Klimas et al, 1994;Koenig et al, 1995b;Tsoukas et al, 2001). In addition, low-dose aldesleukin, a modified form of rhuIL-2, has been used successfully to support adoptively transferred MART-1 specific CTL clones in metastatic melanoma patients (Yee et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: Lack of correlation between in vitro activity and in vivo efficacy

Mealey

Littke

Leib

et al. 2008

Veterinary Immunology and Immunopathology

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Although CTL are important for control of lentiviruses, including equine infectious anemia virus (EIAV), it is not known if CTL can limit lentiviral replication in the absence of CD4 help and neutralizing antibody. Adoptive transfer of EIAV-specific CTL clones into severe combined immunodeficient (SCID) foals could resolve this issue, but it is not known whether exogenous IL-2 administration is sufficient to support the engraftment and proliferation of CTL clones infused into immunodeficient horses. To address this question we adoptively transferred EIAV Rev-specific CTL clones into four EIAV-challenged SCID foals, concurrent with low-dose aldesleukin (180,000 U/ m 2 ), a modified recombinant human IL-2 (rhuIL-2) product. The dose was calculated based on the specific activity on equine PBMC in vitro, and resulted in plasma concentrations considered sufficient to saturate high affinity IL-2 receptors in humans. Despite specific activity on equine PBMC that was equivalent to recombinant equine IL-2 and another form of rhuIL-2, aldesleukin did not support the engraftment and expansion of infused CTL clones, and control of viral load and clinical disease did not occur. It was concluded that survival of Rev-specific CTL clones infused into EIAVchallenged SCID foals was not enhanced by aldesleukin at the doses used in this study, and that in vitro specific activity did not correlate with in vivo efficacy. Successful adoptive immunotherapy with CTL clones in immunodeficient horses will likely require higher doses of rhuIL-2, co-infusion of CD4+ T lymphocytes, or administration of equine IL-2.

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“…However, while these factors may inhibit HIV-1 replication, the inhibition is not mediated at the level of HIV-1 transcription [122,[155][156][157][158][159][160]. activated autologous CD8+ T cells and IL-2 infusion, improvement of oral hairy leukoplakia and Kaposi's sarcoma was observed [185]. [ Only one study has been performed to examine the effects of IL-3 treatment on HIV-1 infection in vivo [186].…”

Section: Modulation Of Hiv-1 Transcription By Cd8+ T Cell-derived Facmentioning

confidence: 99%

Modulation of HIV-1 Transcription by Cytokines and Chemokines

Copeland¹

2005

MRMC

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Infection with HIV results in the modulation of circulating levels of many host factors. Several host proteins that are up-regulated in HIV infection have the potential to influence virus replication. More specifically, the transcription of HIV-1 can be modulated in vivo by host proteins, including cytokines and chemokines. Cytokines modulate transcription mediated by the HIV-1 long terminal repeat (LTR) via multiple signal transduction pathways with resulting recruitment of numerous transcription factors, including NFkappaB, C/EBP, AP-1, TCF-1alpha, NF-IL-6 and ISGF-3. The effects on transcription may vary depending upon the cell type studied and upon the timing of the exposure of infected or transfected cells to cytokines. Furthermore, studies of cytokine mediated activation or inhibition of LTR mediated transcription may also be affected by the presence of the HIV-1 trans-activating protein, Tat, which has significant impact upon the redox state of the cell. This review will examine the complexities of the positive and negative control of HIV transcription by cytokines and chemokines.

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Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion

Cited by 46 publications

References 0 publications

Large-Scale Production of CD4+ T Cells from HIV-1-Infected Donors After CD3/CD28 Costimulation*

Large-Scale Production of CD4+ T Cells from HIV-1-Infected Donors After CD3/CD28 Costimulation*

Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: Lack of correlation between in vitro activity and in vivo efficacy

Modulation of HIV-1 Transcription by Cytokines and Chemokines

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