Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions

Amy J. Miga, Sally R. Masters, Brigit G. Durell, Mercedes Gonzalez, Marc K. Jenkins, Charles Maliszewski, Hitoshi Kikutani, William F. Wade, Randolph J. Noelle

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Inflammatory mediators facilitate the maturation of dendritic cells (DC), enabling them to induce the activation, proliferation and differentiation of cognate T cells. The role of CD40 on DC and CD154 on T cells has been studied by the co-adoptive transfer of antigen-pulsed DC and TCR-transgenic (Tg) T cells in vivo. It is shown that in the absence of CD40-CD154 interactions, initial Tg T cell expansion occurs in vivo, but over time, T cell expansion cannot be sustained. The basis for the demise of the T cell population is likely due to the disappearance of the antigen-pulsed DC in the draining lymph nodes when CD154-CD40 interactions are interrupted. These findings show that both T cell and DC persistence in vivo is dependent on CD40-CD154 interactions. In addition to the physical persistence of the DC, CD40 triggering of DC also greatly increases the period for which they can productively present antigen to Tg T cells. Hence DC persistence and antigen-presenting cell capacity are both dependent on CD40 signaling. While TNF-α can mature DC as measured by a variety of criteria, the unique capacity of CD40 signaling to sustain T cell responses and induce DC maturation is underscored by the inability of TNF-α to rescue the immune deficiency of CD40-/- DC. Hence, the profound impact of CD154 deficiency on cell-mediated immunity may be due to its ability to limit the duration of antigen presentation in vivo and cause the premature demise of antigen-specific T cells.

Original languageEnglish (US)
Pages (from-to)959-965
Number of pages7
JournalEuropean Journal of Immunology
Volume31
Issue number3
DOIs
StatePublished - 2001

Keywords

  • CD40
  • Dendritic cell
  • Th cell

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