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Interleukin-1 production by transformed fibroblasts. II. Influence on antigen presentation and T-cell-mediated anti-tumor response.

Abstract：

:Oncogene-transformed fibroblasts which expressed IL-1, spontaneously or after activation with conditioned medium (CM) and lipopolysaccharide (LPS), regressed in the syngeneic host. Since regression was significantly influenced by the immune competence of the host (see companion report), we speculated that regression was T-cell-mediated. Frequencies of cytotoxic T-cell precursors (CTLp) were in the same range for activated and non-activated, transformed fibroblasts. Furthermore, it was found that lysability of transformed fibroblasts was not influenced by expression of IL-1. These findings exclude the possibility that regression of CM- and LPS-treated transformed fibroblasts may have been due to the appearance of new, strongly immunogenic epitopes. On the other hand, frequencies of CTL were significantly increased after in vivo immunization with IL-1-expressing as compared to IL-1-non-expressing transformed fibroblasts. The in vivo maturation/expansion of CTL could have been the consequence of activation of helper T cells (TH), transformed fibroblast-associated IL-1 delivering the costimulatory signal. Analysis of frequencies and proliferation rates of TH confirmed this assumption. Both parameters were significantly increased after stimulation with transformed fibroblasts expressing IL-1 in comparison to transformed fibroblasts not expressing IL-1. Furthermore, purified T cells apparently depleted of cells expressing MHC class-II antigens, i.e. antigen-presenting cells, proliferated in the presence of transformed fibroblasts expressing IL-1. Since IL-1 rather than MHC class-II antigen expression was the limiting factor, antigen presentation by IL-1-expressing transformed fibroblasts appears unlikely. Instead, maturation of antigen-presenting cells could well have been initiated by tumor-associated IL-1. We conclude that IL-1 expression of transformed fibroblasts plays an important role in the induction of a T-cell-mediated anti-tumor response. The effect is due to increased efficiency in the activation of helper T cells and may be supported by activation of antigen-presenting cells.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Zöller M,Douvdevani A,Segal S,Apte RN

doi

10.1002/ijc.2910500321

keywords:

subject

Has Abstract

pub_date

1992-02-01 00:00:00

pages

450-7

issue

eissn

0020-7136

issn

1097-0215

journal_volume

pub_type

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Interleukin-1 production by transformed fibroblasts. II. Influence on antigen presentation and T-cell-mediated anti-tumor response.