Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs Journal Article

Authors: Nakahara, T.; Uchi, H.; Lesokhin, A. M.; Avogadri, F.; Rizzuto, G. A.; Hirschhorn-Cymerman, D.; Panageas, K. S.; Merghoub, T.; Wolchok, J. D.; Houghton, A. N.
Article Title: Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs
Abstract: Cyclophosphamide (CTX), a commonly used chemotherapeutic agent can enhance immune responses. The ability of CTX to promote the proliferation of effector T cells and abrogate the function of regulatory T cells (Tregs) has been described. In this study, we examined the effects of CTX treatment on dendritic cell (DC) subsets and the subsequent outcome on the effector and suppressive arms of adaptive immunity. In secondary lymphoid tissues, tissue-derived migratory DCs (migratory DCs), lymphoid tissue-resident DCs (resident DCs), and plasmacytoid DCs (pDCs) are well described. CTX has profound and selective cytotoxic effects on CD8+ resident DCs, but not skin-derived migratory DCs or pDCs in lymph nodes (LNs) and spleen, causing an imbalance among these DC subsets. CTX treatment increases the potency of DCs in antigen presentation and cytokine secretion, and partially inhibits the suppressor activity of Tregs. Adoptive transfer of CD8+ DCs can reconstitute this population in regional draining LNs and abrogate the immune-enhancing effects of CTX in vivo. These findings demonstrate that CTX may improve immune responses by preferentially depleting CD8+ lymphoid-resident DCs, which leads to diminished Treg suppression and enhanced effector T-cell function in vivo. © 2010 by The American Society of Hematology.
Keywords: controlled study; nonhuman; lymph nodes; cd8 antigen; animal cell; mouse; animal; cytology; metabolism; animals; mice; animal tissue; biological model; classification; spleen; dendritic cell; animal experiment; cyclophosphamide; cytotoxicity; in vitro study; drug effect; mice, inbred balb c; mice, inbred c57bl; transgenic mouse; c57bl mouse; mice, transgenic; regulatory t lymphocyte; antigen presentation; immunology; mixed lymphocyte culture; dendritic cells; lymphocyte culture test, mixed; bagg albino mouse; t-lymphocytes, regulatory; lymph node; single drug dose; adoptive transfer; immunological adjuvant; adaptive immunity; adjuvants, immunologic; cytokine release; lymphoid tissue; antigens, cd8; plasmacytoid dendritic cell; models, immunological
Journal Title: Blood
Volume: 115
Issue: 22
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-06-03
Start Page: 4384
End Page: 4392
Language: English
DOI: 10.1182/blood-2009-11-251231
PUBMED: 20154220
PROVIDER: scopus
PMCID: PMC2881499
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 20 April 2011" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Jedd D Wolchok
    607 Wolchok
  2. Taha Merghoub
    169 Merghoub
  3. Katherine S Panageas
    312 Panageas
  4. Alan N Houghton
    259 Houghton
  5. Alexander Meyer Lesokhin
    106 Lesokhin
  6. Gabrielle A Rizzuto
    20 Rizzuto