BCG-induced enhancement of endotoxin sensitivity in C3H/HeJ mice. II. T cell modulation of macrophage sensitivity to LPS in vitro

Stefanie N. Vogel, Lynda L. Weedon, L. M. Wahl, D. L. Rosenstreich

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

BCG infection induces a marked increase in LPS sensitivity in vivo and will render genetically defective, LPS hyporesponsive, C3H/HeJ mice almost as sensitive to LPS as normal mice. In this study, we have examined the endotoxin sensitivity of lymphocytes and macrophages from BCG infected mice in order to determine the cellular basis of this effect. We have found that the alteration in endotoxin sensitivity is mediated by a primary effect of BCG infection on T lymphocytes rather than on macrophages. Macrophages from «LPS sensitive», BCG-infected C3H/HeJ mice remain unresponsive to LPS when tested in vitro. However, when peritoneal T lymphocytes from these LPS »corrected» mice were cocultured with LPS unresponsive C3H/HeJ macrophages, a conversion to the LPS-responsive state was observed as manifested by the ability of the macrophages to produce LAF (IL 1) upon LPS stimulation. T cells from normally LPS-responsive or BCG-infected C3H/HeN mice, but not from control C3H/HeJ mice, were also able to render C3H/HeJ macrophages sensitive to LPS. This activity was not affected by treatment of the column-purified T cells with anti-macrophage serum plus complement, indicating that the response was not due to residual LPS-responsive macrophages contaminating the T cell preparations. The ability of the T cell suspension to render C3H/HeJ macrophages capable of producing LAF (IL 1) in response to LPS was abrogated by treatment of the T cell preparations with anti-Thy 1.2 plus complement. These findings establish the importance of T lymphocytes in regulating the LPS sensitivity of macrophages in BCG infected C3H/HeJ mice and support the concept that macrophage LPS responsiveness is dependent upon a certain state of macrophage activation which is regulated by lymphocytes.

Original languageEnglish (US)
Pages (from-to)479-493
Number of pages15
JournalImmunobiology
Volume160
Issue number5
DOIs
StatePublished - Jan 1 1982

Keywords

  • BCG
  • Bacillus Calmette-Guerin
  • LAP (IL 1)
  • LPS
  • PGE
  • Prostaglandin E
  • T cell growth factor or «Interleukin 2»
  • TCGP (IL 2)
  • lipopolysaccharide
  • lymphocyte activating factor or «Interleukin 1»

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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