CELLULAR IMMUNOLOGY 94, 383-393 (1985) Interleukin-2 Apparently Upregulates Its Receptor and Induces Proliferation of Various Resting Mononuclear Leukocytes in the Absence of Antigen’ JOHN M. WILLIAMS,’ MARIO ABBUD-RLHO, VICKI E. KELLEY,~ AND TERRY B. STROM The Charles A. Dana Research Institute, The Harvard-Thorndike Laboratory of the Beth Israel Hospital Department of Medicine, Harvard Medical School and Beth Israel Hospital, Boston, Massachusetts 02215 Received November 30, 1984; accepted May 2, 1985 We demonstrate that exposure to highly purified recombinant interleukin 2 (rIL-2) in the absence of known antigenic stimulation induces/increases the expression of two activation- associated proteins, the interleukin 2 receptor (IL-2R) and 4F2 on “resting” peripheral blood mononuclear cells (PBMC); subsequently, these cells enter the S phase of the cell cycle and proliferate. Dual parameter flow cytometry indicates that the phenotype of the cell population(s) which proliferate following this treatment includes HNK+, DR+, and T3+ cells. A twofold expansion in the number of HNK+ and DR+ cells was observed upon culturing resting PBMC in rIL-2 over a 6-day culture period. While the HNK monoclonal antibody is not specific for NK cells, these data do suggestthat antigen independent growth of HNK+ cells may represent an additional mechanism by which IL2 enhances NK effector activity, i.e., by induction of clonal growth of NK cells. In contrast, several concentrations of recombinant Interferon-y failed to produce a similar proliferative response. 0 1985 Academic Ress, IIIC. INTRODUCTION Multiple signals are required to drive lymphocytes from the resting into the cycling state. Stimulation with antigen or mitogens is necessary for de nova expression of T- and B-lymphocyte membrane receptors for growth factors. One lymphokine, interleukin 2 (IL-2)4 is required for T-cell proliferation (1, 2), while another lymphokine, Interferon-y (IFN-7) has been implicated in the generation of IL-2 receptors as well as in the modulation of natural killer cell (NK) activity ’ This work was supported by grants from: NIH Contract NOI-AI-32687 and NIH AM3392 I (T.B.S.); Pfeiffer Research Foundation (J.M.W.). ‘To whom correspondence should be addressed: Department of Medicine, Renal Unit, Beth Israel Hospital, 330 Brookline Avenue, Boston, Mass. 02215. 3 Present address:Department of Medicine, Laboratory of Immunogenetics & Transplantation, Brigham & Women’s Hospital, Boston, Mass. 02215. 4 Abbreviations used: IL-2, interleukin-2; r&2, recombinant IL-2; IFN-7, Interferon-y; rIFN-y, recombinant IFN-+r; PBMC, peripheral blood mononuclear cells; NHS, pooled normal human AB serum; AHS, autologous human serum; NW, nylon wool; CAM, fluoroscein isothiocyanate goat anti-mouse immunoglobulin; IFLU, immunofluorescence. 383 0008-8749185 $3.00 Copyright Q 1985 by Academic Press, Inc. AU rights of reproduction in any form reserved.