Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. 2010

Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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.

UI MeSH Term Description Entries
D007959 Lymphocyte Culture Test, Mixed Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens. Leukocyte Culture Test, Mixed,Mixed Lymphocyte Culture Test,Mixed Lymphocyte Reaction,Mixed Leukocyte Culture Test,Mixed Leukocyte Reaction,Leukocyte Reaction, Mixed,Leukocyte Reactions, Mixed,Lymphocyte Reaction, Mixed,Lymphocyte Reactions, Mixed,Mixed Leukocyte Reactions,Mixed Lymphocyte Reactions
D008198 Lymph Nodes They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system. Lymph Node,Node, Lymph,Nodes, Lymph
D008221 Lymphoid Tissue Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS. Lymphatic Tissue,Lymphatic Tissues,Lymphoid Tissues,Tissue, Lymphatic,Tissue, Lymphoid,Tissues, Lymphatic,Tissues, Lymphoid
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D005260 Female Females
D000276 Adjuvants, Immunologic Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants

Related Publications

Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
June 2008, Nature immunology,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
December 2023, Journal of the American Heart Association,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
June 2015, Genes to cells : devoted to molecular & cellular mechanisms,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
March 2020, Journal of immunology (Baltimore, Md. : 1950),
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
January 2015, Frontiers in immunology,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
April 1997, Immunological reviews,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
August 2003, Current opinion in immunology,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
January 2023, Journal of microscopy and ultrastructure,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
September 2004, Cytometry. Part A : the journal of the International Society for Analytical Cytology,
Takeshi Nakahara, and Hiroshi Uchi, and Alexander M Lesokhin, and Francesca Avogadri, and Gabrielle A Rizzuto, and Daniel Hirschhorn-Cymerman, and Katherine S Panageas, and Taha Merghoub, and Jedd D Wolchok, and Alan N Houghton
December 2015, Journal of controlled release : official journal of the Controlled Release Society,
Copied contents to your clipboard!