CD28 loss in senescent CD4+ T cells: Reversal by interleukin-12 stimulation

Kenneth J Warrington, Abbe N. Vallejo, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

CD28 is the quintessential costimulatory molecule expressed on CD4+ and CD8+ T cells. During chronic infections and the normal aging process, CD28 expression is lost, compromising the functional activity of T cells. CD28 loss is promoted by replicative stress, particularly in the presence of tumor necrosis factor-α, owing to an inoperative CD28 initiator element. It is currently unknown whether CD28 loss is irreversible. The present study examined cytokines for their ability to reinduce CD28 expression. CD4+CD28null T cells constitutively expressed interleukin-12 (IL-12) α and β receptors, which were functional and allowed for the up-regulation of the signal transducer and activator of transcription-4 (STAT-4)-dependent gene CD161. Costimulation of the T-cell and IL-12 receptors induced the transcription of CD28 in approximately 50% of CD4+CD28null T-cell clones and lines. IL-12 by itself did not restore CD28 expression. Up-regulation of CD28 after IL-12 exposure correlated with the reassembly of the CD28-initiator protein complex. The re-expressed CD28 was functional and restored the ability of CD4+CD28null T cells to express CD25 and CD40 ligand. Our data suggest that IL-12 may, in part, functionally rescue senescent CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)3543-3549
Number of pages7
JournalBlood
Volume101
Issue number9
DOIs
StatePublished - May 1 2003
Externally publishedYes

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T-cells
Interleukin-12
T-Lymphocytes
Interleukin-12 Receptors
STAT4 Transcription Factor
Up-Regulation
CD40 Ligand
Transcription
Clone Cells
Tumor Necrosis Factor-alpha
Genes
Aging of materials
Cytokines
Cell Line
Molecules
Infection

ASJC Scopus subject areas

  • Hematology

Cite this

CD28 loss in senescent CD4+ T cells : Reversal by interleukin-12 stimulation. / Warrington, Kenneth J; Vallejo, Abbe N.; Weyand, Cornelia M.; Goronzy, Jörg J.

In: Blood, Vol. 101, No. 9, 01.05.2003, p. 3543-3549.

Research output: Contribution to journalArticle

Warrington, Kenneth J ; Vallejo, Abbe N. ; Weyand, Cornelia M. ; Goronzy, Jörg J. / CD28 loss in senescent CD4+ T cells : Reversal by interleukin-12 stimulation. In: Blood. 2003 ; Vol. 101, No. 9. pp. 3543-3549.
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