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Veterinary immunology and immunopathology2007; 121(1-2); 8-22; doi: 10.1016/j.vetimm.2007.07.011

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.

Abstract: 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 (180,000U/m2), 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 EIAV-challenged 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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Publication Date: 2007-07-25 PubMed ID: 17727961PubMed Central: PMC2967287DOI: 10.1016/j.vetimm.2007.07.011Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research essentially explores the efficacy of using low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones when infused to foals suffering from severe combined immunodeficiency. However, the results show that despite the calculated and anticipated effects, the approach did not prove effective in controlling viral load or disease progression.

Objective and Context

  • The research revolves around the usage of CTL (Cytotoxic T Lymphocytes), which play a critical role in neutralizing lentiviruses, including diseases like EIAV (Equine Infectious Anemia Virus). However, the effectiveness of CTL in curbing lentiviral replication remains unclear in the absence of neutralizing antibody and CD4 help.
  • In order to provide an answer, four SCID (Severe Combined Immunodeficient) foals infected with EIAV were injected with EIAV-specific CTL clones and a modified recombinant human IL-2 product, aldesleukin.

Experiment and Methodology

  • The dosage of Aldesleukin was determined based on its specific in vitro activity on equine peripheral blood mononuclear cells (PBMC) and resulted in plasma concentrations assumed sufficient to saturate high affinity IL-2 receptors in humans. Their intent was to measure if this dosage could support the survival and proliferation of the infused CTL clones within immunodeficient horses.

Findings and Results

  • Despite the equivalent specific activity on equine PBMC of aldesleukin and another form of recombinant human IL-2, it was observed that aldesleukin did not assist in the survival and proliferation of the introduced CTL clones in the SCID foals.
  • Moreover, there was no subsequent improvement in controlling the viral load or clinical disease.

Conclusions

  • The researchers concluded that using aldesleukin at the used dosages failed to boost the survival of EIAV-specific CTL clones in SCID foals inflicted with EIAV.
  • Additionally, there was no correlation found between in vitro specific activity and in vivo effectiveness. This suggests that successful therapy involving CTL clones on immunodeficient horses may require higher dosages of recombinant human IL-2, co-infusion of CD4+ T lymphocytes or usage of equine IL-2.

Cite This Article

APA
Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. (2007). 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. Vet Immunol Immunopathol, 121(1-2), 8-22. https://doi.org/10.1016/j.vetimm.2007.07.011

Publication

Veterinary immunology and immunopathology
ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 121
Issue: 1-2
Pages: 8-22

Researcher Affiliations

Mealey, Robert H
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, United States. rhm@vetmed.wsu.edu
Littke, Matt H
    Leib, Steven R
      Davis, William C
        McGuire, Travis C

          MeSH Terms

          • Adoptive Transfer / veterinary
          • Animals
          • Animals, Newborn
          • Body Temperature / drug effects
          • Body Temperature / immunology
          • Cell Survival / immunology
          • Equine Infectious Anemia / immunology
          • Equine Infectious Anemia / therapy
          • Equine Infectious Anemia / virology
          • Female
          • Horses
          • Immunotherapy / methods
          • Immunotherapy / veterinary
          • Infectious Anemia Virus, Equine / immunology
          • Injections, Subcutaneous / veterinary
          • Interleukin-2 / administration & dosage
          • Interleukin-2 / analogs & derivatives
          • Male
          • RNA, Viral / blood
          • RNA, Viral / genetics
          • Recombinant Proteins / administration & dosage
          • Reverse Transcriptase Polymerase Chain Reaction / veterinary
          • Severe Combined Immunodeficiency / immunology
          • Severe Combined Immunodeficiency / veterinary
          • Severe Combined Immunodeficiency / virology
          • T-Lymphocytes, Cytotoxic / immunology
          • T-Lymphocytes, Cytotoxic / virology

          Grant Funding

          • K02 AI073101 / NIAID NIH HHS
          • R21 AI058787 / NIAID NIH HHS
          • AI067125 / NIAID NIH HHS
          • R21 AI058787-02 / NIAID NIH HHS
          • R21 AI060395-02 / NIAID NIH HHS
          • AI058787 / NIAID NIH HHS
          • R21 AI060395 / NIAID NIH HHS
          • R21 AI067125 / NIAID NIH HHS
          • R21 AI067125-02 / NIAID NIH HHS
          • AI060395 / NIAID NIH HHS

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