B220+ double-negative T cells suppress polyclonal T cell activation by a fas-independent mechanism that involves inhibition of IL-2 production

Abdel R Hamad, Abdiaziz S. Mohamood, Crystal J. Trujillo, Ching Tai Huang, Emily Yuan, Jonathan P Schneck

Research output: Contribution to journalArticle

Abstract

Fas-mediated apoptosis is a key mechanism for elimination of autoreactive T cells, yet loss of function mutations in the Fas signaling pathway does not result in overt T cell-mediated autoimmunity. Furthermore, mice and humans with homozygous Faslpr or Fas ligandgld mutations develop significant numbers of B220+ CD4- CD8- double-negative (DN) αβ T cells (hereafter referred to as B220 + DN T cells) of poorly understood function. In this study, we show that B220+ DN T cells, whether generated in vitro or isolated from mutant mice, can suppress the ability of activated T cells to proliferate or produce IL-2, IL-10, and IFN-γ B220+ DN T cells that were isolated from either lpr or gld mice were able to suppress proliferation of autologous and syngeneic CD4 T cells, showing that suppression is Fas independent. Furthermore, restoration of Fas/Fas ligand interaction did not enhance suppression. The mechanism of suppression involves inhibition of IL-2 production and its high affinity IL-2R α-chain (CD25). Suppression also requires cell/cell contact and TCR activation of B220+ DN T cells, but not soluble cytokines. These findings suggest that B220+. DN T cells may be involved in controlling autoreactive T cells in the absence of Fas-mediated peripheral tolerance.

Original languageEnglish (US)
Pages (from-to)2421-2426
Number of pages6
JournalJournal of Immunology
Volume171
Issue number5
StatePublished - Sep 1 2003

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Interleukin-2
T-Lymphocytes
Peripheral Tolerance
Mutation
Fas Ligand Protein
Autoimmunity
Interleukin-10
Apoptosis
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

B220+ double-negative T cells suppress polyclonal T cell activation by a fas-independent mechanism that involves inhibition of IL-2 production. / Hamad, Abdel R; Mohamood, Abdiaziz S.; Trujillo, Crystal J.; Huang, Ching Tai; Yuan, Emily; Schneck, Jonathan P.

In: Journal of Immunology, Vol. 171, No. 5, 01.09.2003, p. 2421-2426.

Research output: Contribution to journalArticle

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AU - Mohamood, Abdiaziz S.

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AU - Huang, Ching Tai

AU - Yuan, Emily

AU - Schneck, Jonathan P

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