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Journal of immunology (Baltimore, Md. : 1950)1987; 139(1); 61-67;

Large granular lymphocytes from SCID horses develop potent cytotoxic activity after treatment with human recombinant interleukin 2.

Abstract: Peripheral blood mononuclear cells from foals with hereditary severe combined immunodeficiency (SCID) have morphologic characteristics of large granular lymphocytes (LGL). Attempts to demonstrate cytotoxic activity were without success unless the LGL were incubated with 100 U of human recombinant interleukin 2 (rIL 2)/ml for 24 hr. With rIL 2 incubation, low effector to target ratios (10:1) consistently yielded high levels of cytotoxic activity (30 to 50%) in a standard 4-hr 51Cr-release assay using YAC-1 lymphoma or K562 erythroleukemia cell lines as targets. Monoclonal antibody EqT12 reacted with a large percentage of these cells, and the level of cytotoxic activity was directly correlated to the percentage of EqT12+ cells in the preparation. In normal horses, the percentage of circulating EqT12+ cells is low (5%), while at the same time, cytotoxic activity is not usually detectable even with rIL 2 incubation. In contrast, the percentage of EqT12+ cells in blood of SCID horses is high (up to 40%), as is the IL 2-inducible cytotoxic activity. These results indicate that cytotoxic cells with morphologic and functional characteristics of natural killer cells are produced by horses with SCID.
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Publication Date: 1987-07-01 PubMed ID: 3108403
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

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 study explores the ability of large granular lymphocytes (LGL) from horses with severe combined immunodeficiency (SCID) to develop cytotoxic activity when treated with human recombinant interleukin 2 (rIL 2). It found a significant increase in cytotoxic activity under these conditions, indicating that horses with SCID can produce cytotoxic cells similar to natural killer cells.

Objective and Methodology

  • The main objective of this study was to investigate the cytotoxicity of Large granular lymphocytes (LGL) from SCID horses once treated with human recombinant interleukin 2 (rIL 2).
  • Peripheral blood mononuclear cells from SCID foals were used in the investigation, with an attempt to demonstrate cytotoxic activity.
  • The LGL were incubated with 100 U of rIL 2/ml for 24 hours. Post-incubation, 51Cr-release assay was performed to measure cytotoxic activity against YAC-1 lymphoma or K562 erythroleukemia cell lines.

Results and Findings

  • Without the rIL 2 incubation, attempts to show cytotoxic activity were unsuccessful.
  • With rIL 2 incubation, there was a consistent display of high levels of cytotoxic activity. Specifically, low effector to target ratios (10:1) yielded cytotoxic activity levels of 30 to 50%.
  • The monoclonal antibody EqT12 reacted with a large percentage of these cells, and it was found that the level of cytotoxic activity was directly related to the percentage of EqT12+ cells in the preparation.
  • In normal horses, the percentage of circulating EqT12+ cells is low (5%) and cytotoxic activity is not usually detectable even with rIL 2 incubation.
  • In contrast, the percentage of EqT12+ cells in the blood of SCID horses is high (up to 40%). Likewise, the IL 2-inducible cytotoxic activity is also high in SCID horses.

Conclusions

  • These findings indicate that horses with SCID can produce cytotoxic cells with morphologic and functional characteristics similar to natural killer (NK) cells.
  • The research contributes to a greater understanding of the immune system’s response and functionality within SCID horses, particularly regarding the role of LGL and rIL 2 in cytotoxic activity.

Cite This Article

APA
Magnuson NS, Perryman LE, Wyatt CR, Mason PH, Talmadge JE. (1987). Large granular lymphocytes from SCID horses develop potent cytotoxic activity after treatment with human recombinant interleukin 2. J Immunol, 139(1), 61-67.

Publication

Journal of immunology (Baltimore, Md. : 1950)
ISSN: 0022-1767
NlmUniqueID: 2985117R
Country: England
Language: English
Volume: 139
Issue: 1
Pages: 61-67

Researcher Affiliations

Magnuson, N S
    Perryman, L E
      Wyatt, C R
        Mason, P H
          Talmadge, J E

            MeSH Terms

            • Animals
            • Antigens, Differentiation, T-Lymphocyte
            • Antigens, Surface / analysis
            • Cell Differentiation
            • Cytotoxicity, Immunologic
            • Horse Diseases / immunology
            • Horses / immunology
            • Immunity, Cellular
            • Immunologic Deficiency Syndromes / immunology
            • Immunologic Deficiency Syndromes / veterinary
            • Interleukin-2 / pharmacology
            • Killer Cells, Natural / classification
            • Killer Cells, Natural / immunology
            • Lymphocytes / classification
            • Lymphocytes / immunology
            • Recombinant Proteins / pharmacology
            • T-Lymphocytes / classification
            • T-Lymphocytes / immunology

            Grant Funding

            • AI 07025 / NIAID NIH HHS
            • HD 08886 / NICHD NIH HHS

            Citations

            This article has been cited 7 times.
            1. Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. 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 2008 Jan 15;121(1-2):8-22.
              doi: 10.1016/j.vetimm.2007.07.011pubmed: 17727961google scholar: lookup
            2. Mealey RH, Leib SR, Pownder SL, McGuire TC. Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection. J Virol 2004 Sep;78(17):9295-305.
              doi: 10.1128/JVI.78.17.9295-9305.2004pubmed: 15308724google scholar: lookup
            3. Evans DL, Jaso-Friedmann L. Natural killer (NK) cells in domestic animals: phenotype, target cell specificity and cytokine regulation. Vet Res Commun 1993;17(6):429-47.
              doi: 10.1007/BF01839211pubmed: 8030197google scholar: lookup
            4. Perryman LE, Mason PH, Chrisp CE. Effect of spleen cell populations on resolution of Cryptosporidium parvum infection in SCID mice. Infect Immun 1994 Apr;62(4):1474-7.
              doi: 10.1128/iai.62.4.1474-1477.1994pubmed: 7907581google scholar: lookup
            5. Lunn DP, McClure JT, Schobert CS, Holmes MA. Abnormal patterns of equine leucocyte differentiation antigen expression in severe combined immunodeficiency foals suggests the phenotype of normal equine natural killer cells. Immunology 1995 Mar;84(3):495-9.
              pubmed: 7751035
            6. Perryman LE, O'Rourke KI, McGuire TC. Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. J Virol 1988 Aug;62(8):3073-6.
              doi: 10.1128/JVI.62.8.3073-3076.1988pubmed: 2839723google scholar: lookup
            7. Trinchieri G. Biology of natural killer cells. Adv Immunol 1989;47:187-376.
              doi: 10.1016/s0065-2776(08)60664-1pubmed: 2683611google scholar: lookup
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