Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions.
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-alpha 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-alpha 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.
Department of Microbiology, Dartmouth Medical School, Lebanon, USA.
A J
AJ
Miga
S R
SR
Masters
B G
BG
Durell
M
M
Gonzalez
M K
MK
Jenkins
C
C
Maliszewski
H
H
Kikutani
W F
WF
Wade
R J
RJ
Noelle
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D002454:Cell Differentiation; D017635:Clonal Anergy; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019013:CD40 Antigens; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12