B7-H1 expression on old CD8+ T cells negatively regulates the activation of immune responses in aged animals

Noweeda Mirza, Maria Adelaida Duque, Ana Lucia Dominguez, Adam G. Schrum, Haidong Dong, Joseph Lustgarten

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

T cell responses are compromised in the elderly. The B7-CD28 family receptors are critical in the regulation of immune responses. We evaluated whether the B7-family and CD28-family receptors were differentially expressed in dendritic cells, macrophages, and CD4+ and CD8+ T cells from young and old mice, which could contribute to the immune dysfunction in the old. Although most of the receptors were equally expressed in all cells, >85% of the old naive CD8+ T cells expressed B7-H1 compared with 25% in the young. Considering that B7-H1 negatively regulates immune responses, we hypothesized that expression of B7-H1 would downregulate the function of old CD8+ T cells. Old CD8+ T cells showed reduced ability to proliferate, but blockade of B7-H1 restored the proliferative capacity of old CD8+ T cells to a level similar to young CD8+ T cells. In vivo blockade of B7-H1 restored antitumor responses against the B7-H1 - BM-185-enhanced GFP tumor, such that old animals responded with the same efficiency as young mice. Our data also indicate that old CD8+ T cells express lower levels of TCR compared with young CD8+ T cells. However, following antigenic stimulation in the presence of B7-H1 blockade, the levels of TCR expression were restored in old CD8+ T cells, which correlated with stronger T cell activation. These studies demonstrated that expression of B7-H1 in old CD8+ T cells impairs the proper activation of these cells and that blockade of B7-H1 could be critical to optimally stimulate a CD8 T cell response in the old.

Original languageEnglish (US)
Pages (from-to)5466-5474
Number of pages9
JournalJournal of Immunology
Volume184
Issue number10
DOIs
StatePublished - May 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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