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

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.

CD40/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell‐produced IL‐2

“…CD40 triggering has been shown to promote DC survival during cognate interaction with CD4 + T cells in vivo; indeed CD40KO DC live no more than five days after initial encounter with T cell and are no longer available for persisting T cell stimulation [37]. We cannot exclude that a shorten interaction between DC and T reg in vivo could contribute to the observed T reg defects in absence of CD40.…”

Cognate interactions between memory T cells and tumor antigen‐presenting dendritic cells from bone marrow of breast cancer patients: Bidirectional cell stimulation, survival and antitumor activity in vivo

“…40 Furthermore, DC longevity and T-cell persistence was reported to be controlled by CD40-CD154 interactions. 41 Recently, it was reported that antigen-presenting DCs (i) provide the reducing extracellular microenvironment required for T-lymphocyte activation 42 and (ii) control T-cell proliferation by regulating amino acid availability. 43 To prevent activation-induced cell death, 44,45 memory T cells might upregulate anti-apoptotic genes.…”

Genetic Disassociation of Autoimmunity and Resistance to Costimulation Blockade-Induced Transplantation Tolerance in Nonobese Diabetic Mice

“…Dendritic cells are regulators of immunity and self tolerance (37,38) and play an important role in transplantation tolerance (39 -41). Maturation of dendritic cells is dependent on CD40-CD154 interaction (42), and NOD mice reportedly exhibit abnormalities in dendritic cell maturation (12, 43-48). Life table analysis of skin allograft survival in mice treated with DST plus anti-CD154 mAb.…”