Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells

Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3669-74. doi: 10.1073/pnas.93.8.3669.

Abstract

We show that interleukin 3 (IL-3) enhances the generation of tumor-specific cytotoxic T lymphocytes (CTLs) through the stimulation of host antigen-presenting cells (APCs). The BALB/c (H-2d) spontaneous lung carcinoma line 1 was modified by gene transfection to express ovalbumin as a nominal "tumor antigen" and to secrete IL-3, a cytokine enhancing myeloid development. IL-3-transfected tumor cells are less tumorigenic than the parental cell line, and tumor-infiltrating lymphocytes isolated from these tumors contain increased numbers of tumor-specific CTLs. By using B3Z86/90.14 (B3Z), a unique T-cell hybridoma system restricted to ovalbumin/H-2b and implanting the tumors in (BALB/c x C57BL/6)F1 (H-2d/b) mice, we demonstrate that the IL-3-transfected tumors contain an increased number of a rare population of host cells that can process and "re-present" tumor antigen to CTLs. Electron microscopy allowed direct visualization of these host APCs, and these studies, along with surface marker phenotyping, indicate that these APCs are macrophage-like. The identification of these cells and their enhancement by IL-3 offers a new opportunity for tumor immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / ultrastructure
  • Antigens, Neoplasm / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Hybridomas
  • Immunotherapy
  • Interleukin-3 / pharmacology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / ultrastructure
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Immunoelectron
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Phenotype
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Histocompatibility Antigens Class I
  • Interleukin-3
  • Ovalbumin