Human purified protein derivative-specific CD4+ T cells use both CD95- dependent and CD95-independent cytolytic mechanisms

David Lewinsohn, Teresa T. Bement, Jiangchun Xu, David H. Lynch, Kenneth H. Grabstein, Steven G. Reed, Mark R. Alderson

Research output: Contribution to journalArticle

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Abstract

CTL, both CD4+ and CD8+, are essential in the eradication of intracellular pathogens. Data generated using murine T cells have suggested a critical role for CD95 (Fas, Apo-1) in CD4+ T cell-induced apoptosis of target cells. In contrast, CD8+ CTL predominantly use the perforin/granzyme lytic pathway. At present little is known about the mechanism of CD4+ CTL lytic function during intracellular infection in humans. We have used human CD4+ T cells specific for purified protein derivative (PPD) of Mycobacterium tuberculosis to explore whether CD95 is the dominant cytolytic mechanism. PPD-reactive CD4+ clones efficiently lysed Ag-pulsed autologous monocytes, adherent macrophages, and EBV-transformed B cells. Addition of an antagonistic CD95 Ab had a minimal effect on cytolysis, whereas addition of MgEGTA to block perforin/granzyme resulted in complete inhibition of killing. In contrast, lysis of activated peripheral blood B cells could be partially blocked with the antagonistic CD95 Ab. Supporting these observations, monocytes, macrophages, and EBV-transformed B cells were not lysed by an agonistic CD95 Ab. Activated B cells were readily lysed by the agonistic CD95 Ab. T cell clones triggered through the TCR with anti-CD3 were capable of lysing the CD95-sensitive Jurkat T cell line in a CD95-dependent manner, but were also able to release granzymes. We conclude that human CD4+ T cells are capable of lysing PPD-pulsed targets using both perforin/granzyme and CD95 pathways. The contribution of CD95 is strictly dependent on target cell susceptibility to CD95-mediated killing.

Original languageEnglish (US)
Pages (from-to)2374-2379
Number of pages6
JournalJournal of Immunology
Volume160
Issue number5
StatePublished - Mar 1 1998
Externally publishedYes

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Granzymes
T-Lymphocytes
Perforin
B-Lymphocytes
Proteins
Human Herpesvirus 4
Monocytes
Clone Cells
Macrophages
Jurkat Cells
Mycobacterium tuberculosis
Blood Cells
Apoptosis
Cell Line
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Lewinsohn, D., Bement, T. T., Xu, J., Lynch, D. H., Grabstein, K. H., Reed, S. G., & Alderson, M. R. (1998). Human purified protein derivative-specific CD4+ T cells use both CD95- dependent and CD95-independent cytolytic mechanisms. Journal of Immunology, 160(5), 2374-2379.

Human purified protein derivative-specific CD4+ T cells use both CD95- dependent and CD95-independent cytolytic mechanisms. / Lewinsohn, David; Bement, Teresa T.; Xu, Jiangchun; Lynch, David H.; Grabstein, Kenneth H.; Reed, Steven G.; Alderson, Mark R.

In: Journal of Immunology, Vol. 160, No. 5, 01.03.1998, p. 2374-2379.

Research output: Contribution to journalArticle

Lewinsohn, D, Bement, TT, Xu, J, Lynch, DH, Grabstein, KH, Reed, SG & Alderson, MR 1998, 'Human purified protein derivative-specific CD4+ T cells use both CD95- dependent and CD95-independent cytolytic mechanisms', Journal of Immunology, vol. 160, no. 5, pp. 2374-2379.
Lewinsohn, David ; Bement, Teresa T. ; Xu, Jiangchun ; Lynch, David H. ; Grabstein, Kenneth H. ; Reed, Steven G. ; Alderson, Mark R. / Human purified protein derivative-specific CD4+ T cells use both CD95- dependent and CD95-independent cytolytic mechanisms. In: Journal of Immunology. 1998 ; Vol. 160, No. 5. pp. 2374-2379.
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