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Involvement of Both Tac and Non-Tac Interleukin 2-binding Peptides in the Interleukin 2-dependent Proliferation of Human Tumor-infiltrating Lymphocytes¹

Departments of Tumor Biology [M. Y., L. B. O-S., E. A. G.], General Surgery [K. I., C. M. B., E. A. G.], and Immunology [C. D. P.], U.T.M.D. Anderson Hospital and Cancer Center, Houston, Texas 77030, and Metabolism Branch, National Cancer Institute, Bethesda, Maryland 20892 [M. T.]

Interleukin 2 (IL-2) receptor expression was examined on recombinant IL-2 (rIL-2)-propagated tumor-infiltrating lymphocytes (TIL) from eight metastatic melanoma and three sarcoma samples. All 11 TIL expanded with similar growth rates. rIL-2 propagated TIL from five of eight metastatic melanoma specimens contained no Tac antigen-positive lymphocytes as determined by immunofluorescence and flow cytometry performed multiple times during the 4 to 8 week culture period. However, "Tac-negative" TIL did express the non-Tac IL-2-binding peptide, p70–75 as determined by [¹²⁵I]IL-2 cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IL-2-binding assays revealed that these "Tac-negative" TIL expressed only an intermediate affinity IL-2 receptor. In contrast, TIL from the other three of eight melanoma and all three sarcoma contained one-third Tac-positive cells as assessed by flow cytometry analysis, and expressed surface non-Tac (p70–75) and Tac (p55) peptides by [¹²⁵I]IL-2 cross-linking. These "Tac-positive" TIL displayed both the high and intermediate affinity IL-2 receptors. However, rIL-2-dependent growth of both "Tac-negative" and "Tac-positive" TIL was significantly inhibited by anti-Tac mAb, suggesting a transient Tac expression on the "Tac-negative" TIL. Additionally, due to the limits of our methodology, we cannot rule out the possibility of a constitutive expression of a low level of Tac, with an indicible expression of higher levels. Addition of culture supernatants from phytohemagglutinin- and phorbol myristate acetate-stimulated peripheral blood mononuclear cells to the "Tac-negative" TIL-induced detectable Tac expression within 48 h. These results indicate that both non-Tac and Tac IL-2 receptors play important roles during IL-2-dependent proliferation of TIL.

¹ This work was supported in part by NIH Grant 5511-25 (to K. I.), a grant (CH-420) from the American Cancer Society, and by grants from the Eleanor Naylor Dana Trust (to C. D. P.), the Edwin Zaban Melanoma Research Fund, the Meadows Foundation (to C. M. B.), and by NCI Grant ROI-Ca45225 (to E. A. G.).

² Present address: Department of Pathology, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland.

³ To whom requests for reprints should be addressed, at Department of Tumor Biology, Box 79, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 6/23/88. Revised 11/28/88. Accepted 12/ 2/88.