Class i and ii mhc restricted cytotox1city of alveolar lymphocytes for macrophages infected with micobacterium tuberculosis or exposed to its purified protein derivative

I. S. Jian, W. H. Boom, S. K. Schwander, K. N. Balaji, E. A. Rich

Research output: Contribution to journalArticle

Abstract

Cytotoxicity against Mycobacterium tuberculosis (MTB) infected macrophages may be a mechanism of host defense. Thus, the capacity of alveolar lymphocytes (AL) and alveolar macrophages (AM) from tuberculin skin test positive healthy subjects to serve as cytotoxic T lymphocytes (CTLs) and target cells, respectively, in response to MTB (H37Ra) or purified protein derivative (PPD) was investigated using a 51Cr release assay. AM infected with MTB or stimulated with PPD were targets of blood CTL activity (up to 20% specific cytotoxicity) at effector to target ratios (E:T) of 10:1 and higher (p < 0.01). Blood CTL activity was predominantly restricted to class II MHC and was adhesion (ICAM/LFA-1) molecule dependent AM were, however, more resistant to cytotoxicity than autologous blood monocytes which were targets of CTL activity at lower E:T ratios (1:1) and with greater specific cytotoxicity (to 30%). To examine CTL activity of AL, bronchoalveolar cells were stimulated with PPD plus IL-2 for 7-10 days. AL were cytotoxic for autologous mycobacterial stimulated blood monocytes at E:T ratios of 10:1 and higher (similar to blood lymphocytes) (p < 0.01). CTL activity of AL required cell adhesion molecules and was both class I and class II MHC restricted. Both CD4+ and CD8+ AL were expanded by stimulation with PPD and IL-2. Furthermore, sorting of these phenotypes using antibody coated magnetic beads demonstrated that both CD4+ and CD8+ AL had CTL activity for PPD stimulated and for MTB-infected monocytes. Thus, AL are capable of both Class I and II MHC dependent CTL activity against MTB infected or PPD-stimulated macrophages. Such novel cytotoxic responses may be a major mechanism of defense against MTB at the site of disease activity.

Original languageEnglish (US)
Pages (from-to)217a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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