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. 1987 Dec 1;166(6):1716-33.
doi: 10.1084/jem.166.6.1716.

Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection

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Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection

J S Weber et al. J Exp Med. .

Abstract

We have shown that two weakly immunogenic MCA sarcomas developed in our laboratory that are sensitive to high-dose IL-2 immunotherapy express class I MHC in vivo and in vitro. Two nonimmunogenic MCA sarcomas are relatively insensitive to IL-2 therapy and express minimal or no class I MHC molecules in vivo and in vitro. To study the role of MHC in the therapy of tumors with IL-2, a class I-deficient murine melanoma, B16BL6, was transfected with the Kb class I gene. Expression of class I MHC rendered B16BL6 advanced pulmonary macrometastases sensitive to IL-2 immunotherapy. 3-d micrometastases of CL8-2, a class I transfected clone of B16BL6, were significantly more sensitive to IL-2 therapy than a control nontransfected line. Expression of Iak, a class II MHC molecule, had no effect on IL-2 therapy of transfectant pulmonary micrometastases in F1 mice. By using lymphocyte subset depletion with mAbs directed against Lyt-2, therapy of class I transfectant macrometastases with high-dose IL-2 was shown to involve an Lyt-2 cell. In contrast, regression of micrometastases treated with low-dose IL-2 involved Lyt-2+ cells, but regression mediated by high doses of IL-2 did not. We hypothesize that both LAK and Lyt-2+ T cells effect IL-2-mediated elimination of micrometastases, but only Lyt-2+ T cells are involved in macrometastatic regression. Low doses of IL-2 stimulate Lyt-2+ cells to eliminate class I-expressing micrometastases, but high doses of IL-2 can recruit LAK cells to mediate regression of micrometastases independent of class I expression. Only high-dose IL-2, mediating its effect predominantly via Lyt-2+ cells, is capable of impacting on MHC class I-expressing macrometastases. Macrometastases devoid of class I MHC antigens appear to be resistant to IL-2 therapy.

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References

    1. J Immunol. 1983 May;130(5):2471-8 - PubMed
    1. J Immunol. 1987 Jul 1;139(1):285-94 - PubMed
    1. J Am Acad Dermatol. 1983 Dec;9(6):867-71 - PubMed
    1. Science. 1984 Mar 30;223(4643):1412-4 - PubMed
    1. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4080-4 - PubMed

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