Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization

Barbon, Christine M.; Yang, Min; Wands, Gregory D.; Ramesh, Radha; Slusher, Barbara S.; Hedley, Mary Lynne; Luby, Thomas M.

doi:10.1016/j.cellimm.2010.02.007

Cited by 35 publications

(31 citation statements)

References 65 publications

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“…Intraperitoneal injection of CTX (200 mg/kg) significantly reduced the number of CD4 + and CD8 + T cells in the spleen and lymph nodes of Balb/c mice on days 3 and 5, but did not decrease their percentage [22]. The substantial loss of CD4 + and CD8 + subsets was observed in the spleens of C3HeB/FeJ (H-2 k) mice treated with a single dose of CTX at 100 or 200 mg/kg within 5 days, and more modest cell loss was detected in animals dosed with 5 consecutive daily injections at 20 mg/kg [23].…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice

Huyan

Gao

et al. 2011

International Immunopharmacology

115

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There has been lack of the uniform standard for establishment of animal immunodepressive models induced by cyclophosphamide (CTX), and the information about the immunosuppressive effect of CTX on peripheral blood lymphocyte subsets in rodents. Here we describe a CTX-induced mouse model and try to establish a feasible immunosuppressive model for studying the fungal pathogenicity. Balb/c mice received two intraperitoneal injections of different CTX doses (50-200 mg/kg) at 2-day intervals. Peripheral whole blood collected at different time-points before and after CTX injection was used to detect white blood cells (WBCs), lymphocytes and their subsets by automated hematology analyzer and flow cytometry, respectively. WBCs and lymphocytes in all groups except CTX50 (50 mg/kg CTX) group commenced to decrease in a dose-dependent manner on day 1, reached the nadir on day 4, rebounded on day 10, and declined again on day 17 after CTX treatment. Low dose (50 mg/kg) CTX produced no obvious change of percentage of CD3(+), CD4(+) and CD8(+) T cells and CD19(+) cells, but high doses (100 or 150 mg/kg) yielded a significant decrease of CD3(+) and CD4(+) cells on day 4 and CD19(+) cells on day 10, and increase of CD8(+) cells on day 4. The CD4(+)/CD8(+) ratio decreased on day 4, followed by a rebound thereafter when treated with 3 different doses of CTX. The results indicate that two intraperitoneal injections of CTX at 150 mg/kg at 2-day intervals may establish good immunosuppressive models of Balb/c mice for studying the fungal pathogenicity.

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Section: Discussionmentioning

confidence: 99%

Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice

Huyan

Gao

et al. 2011

International Immunopharmacology

115

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“…Since Treg depletion can enhance inflammation and autoimmunity then such transient depletion, as opposed to long term effects, is desirable. In low doses, the agent cyclophosphamide transiently decreases Treg frequencies while Teff functions are preserved, leading to enhanced responses to vaccine antigens and improved vaccine immunogenicity in mouse and human cancer vaccine trials (Barbon et al, 2010; Le and Jaffee, 2012). Anti-CD25 monoclonal antibodies, which deplete Tregs in vivo , enhanced vaccine efficacy in mouse models of pancreatic carcinoma (Keenan et al, 2014) and melanoma (Tan et al, 2013).…”

Section: Targeting Tregs In Vivo To Enhance Vaccine Immunogenicitymentioning

confidence: 99%

Targeting regulatory T cells to improve vaccine immunogenicity in early life

Ndure

Flanagan

2014

Front. Microbiol.

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Human newborns and infants are bombarded with multiple pathogens on leaving the sterile intra-uterine environment, and yet have suboptimal innate immunity and limited immunological memory, thus leading to increased susceptibility to infections in early life. They are thus the target age group for a host of vaccines against common bacterial and viral pathogens. They are also the target group for many vaccines in development, including those against tuberculosis (TB), malaria, and HIV infection. However, neonatal and infant responses too many vaccines are suboptimal, and in the case of the polysaccharide vaccines, it has been necessary to develop the alternative conjugated formulations in order to induce immunity in early life. Immunoregulatory factors are an intrinsic component of natural immunity necessary to dampen or control immune responses, with the caveat that they may also decrease immunity to infections or lead to chronic infection. This review explores the key immunoregulatory factors at play in early life, with a particular emphasis on regulatory T cells (Tregs). It goes on to explore the role that Tregs play in limiting vaccine immunogenicity, and describes animal and human studies in which Tregs have been depleted in order to enhance vaccine responses. A deeper understanding of the role that Tregs play in limiting or controlling vaccine-induced immunity would provide strategies to improve vaccine immunogenicity in this critical age group. New adjuvants and drugs are being developed that can transiently suppress Treg function, and their use as part of human vaccination strategies against infections is becoming a real prospect for the future.

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“…This dose had been defined by the DTH test as the optimal immunostimulatory dose of the drug. The second (positive control) and third groups (negative control) intraperitoneally received the same volumes of cyclophosphamide (20 mg/kg/day) [27] and ART diluents (ethanol/PBS), respectively. The treatments were applied for three consecutive days followed by three more administrations on days 5, 7, and 9.…”

Section: Breast Cancer Modelmentioning

confidence: 99%

“…Cancer immunotherapy aims at countering the immunosuppressive moiety of tumor cells and tipping the balance of Th1/Th2 in favor of Th1 antitumor immunity [25,26]. However, most current chemotherapeutic regimens are immunosuppressive and only a few of them, such as cyclophosphamide (CY) [27][28][29], have some 'side effects' on the immune system [30].…”

Section: Introductionmentioning

confidence: 99%

Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo

Farsam

Hassan

Zavaran-Hosseini

et al. 2011

International Immunopharmacology

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Consecutive low doses of cyclophosphamide preferentially target Tregs and potentiate T cell responses induced by DNA PLG microparticle immunization

Cited by 35 publications

References 65 publications

Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice

Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice

Targeting regulatory T cells to improve vaccine immunogenicity in early life

Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo

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