Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist

Larry E. Kahn, Parul Doshi, Kelly L. McGarity, Mingfu Yu, Christine P. Bono, Wen Rong Lie, Anne M. Rankin, Mary L. Smidt, Philip Streeter, Barbara K. Klein, Joseph K. Welply, Susan L. Woulfe

Research output: Contribution to journalArticle

Abstract

Background: Progenipoietin-4 (ProGP-4) is an E. coli derived chimeric growth factor that activates the human Flt3 and G-CSF receptors. ProGP-4 possesses cross-species activity and treatment of mice with ProGP-4 results in increases in the number of WBC and Class II+/CD11c+ cells in both spleen and peripheral blood. Herein, we report morphologic, phenotypic and functional evaluation of Class II+/CD11c+ cells generated by in vivo administration of ProGP-4. Material/Methods: C57BL/6 mice were injected daily with ProGP for 7 to 18 days. Leukocytes from spleen and peripheral blood were analyzed by flow cytometry to enumerate and characterize changes in DC populations. Spleens from ProGP treated mice were evaluated by immunocytochemistry and enriched CD11c+ populations were functionally assessed in a mixed lymphocyte assay and in an antigen dependent CTL assay. Results: Administration of this dual receptor agonist to mice resulted in dose-dependent increases in the numbers of total white blood cells and Class II+/CD11c+ cells in spleen and peripheral blood. CD11c+ cells from ProGP-4 treated mice co-expressed DEC205 and also expressed CD80, CD86 and CD40, albeit at lower levels as compared to Class 11+/CD11c+ cells from untreated animals. Despite lower co-stimulatory molecule expression, ProGP-4-generated Class 11+/CD11c+ cells stimulated proliferation of allogeneic T cells and an antigen-specific T cell hybridoma as efficiently as bone marrow derived dendritic cells from untreated mice. Conclusion: The data presented in this report highlight the ability of E. coli derived ProGP-4 to expand large numbers of functional DC in the peripheral blood and lymphoid organs in vivo using a rodent model of hematopoiesis. E. coli derived chimeric receptor agonists such as ProGP-4 may enable further investigations of imnmnotherapeutic approaches to the treatment of diseases such as cancer and autoimmunity.

Original languageEnglish (US)
JournalMedical Science Monitor
Volume8
Issue number12
StatePublished - Dec 1 2002

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Dendritic Cells
Escherichia coli
Spleen
Leukocytes
Granulocyte Colony-Stimulating Factor Receptors
T-Lymphocytes
Viral Tumor Antigens
Hematopoiesis
Hybridomas
Autoimmunity
Inbred C57BL Mouse
Population
Rodentia
Intercellular Signaling Peptides and Proteins
Flow Cytometry
Bone Marrow
Immunohistochemistry
Cell Proliferation
Lymphocytes
Antigens

Keywords

  • Antigen presentation
  • Cytokine
  • Dendritic cell
  • Immunotherapy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kahn, L. E., Doshi, P., McGarity, K. L., Yu, M., Bono, C. P., Lie, W. R., ... Woulfe, S. L. (2002). Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist. Medical Science Monitor, 8(12).

Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist. / Kahn, Larry E.; Doshi, Parul; McGarity, Kelly L.; Yu, Mingfu; Bono, Christine P.; Lie, Wen Rong; Rankin, Anne M.; Smidt, Mary L.; Streeter, Philip; Klein, Barbara K.; Welply, Joseph K.; Woulfe, Susan L.

In: Medical Science Monitor, Vol. 8, No. 12, 01.12.2002.

Research output: Contribution to journalArticle

Kahn, LE, Doshi, P, McGarity, KL, Yu, M, Bono, CP, Lie, WR, Rankin, AM, Smidt, ML, Streeter, P, Klein, BK, Welply, JK & Woulfe, SL 2002, 'Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist', Medical Science Monitor, vol. 8, no. 12.
Kahn, Larry E. ; Doshi, Parul ; McGarity, Kelly L. ; Yu, Mingfu ; Bono, Christine P. ; Lie, Wen Rong ; Rankin, Anne M. ; Smidt, Mary L. ; Streeter, Philip ; Klein, Barbara K. ; Welply, Joseph K. ; Woulfe, Susan L. / Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist. In: Medical Science Monitor. 2002 ; Vol. 8, No. 12.
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abstract = "Background: Progenipoietin-4 (ProGP-4) is an E. coli derived chimeric growth factor that activates the human Flt3 and G-CSF receptors. ProGP-4 possesses cross-species activity and treatment of mice with ProGP-4 results in increases in the number of WBC and Class II+/CD11c+ cells in both spleen and peripheral blood. Herein, we report morphologic, phenotypic and functional evaluation of Class II+/CD11c+ cells generated by in vivo administration of ProGP-4. Material/Methods: C57BL/6 mice were injected daily with ProGP for 7 to 18 days. Leukocytes from spleen and peripheral blood were analyzed by flow cytometry to enumerate and characterize changes in DC populations. Spleens from ProGP treated mice were evaluated by immunocytochemistry and enriched CD11c+ populations were functionally assessed in a mixed lymphocyte assay and in an antigen dependent CTL assay. Results: Administration of this dual receptor agonist to mice resulted in dose-dependent increases in the numbers of total white blood cells and Class II+/CD11c+ cells in spleen and peripheral blood. CD11c+ cells from ProGP-4 treated mice co-expressed DEC205 and also expressed CD80, CD86 and CD40, albeit at lower levels as compared to Class 11+/CD11c+ cells from untreated animals. Despite lower co-stimulatory molecule expression, ProGP-4-generated Class 11+/CD11c+ cells stimulated proliferation of allogeneic T cells and an antigen-specific T cell hybridoma as efficiently as bone marrow derived dendritic cells from untreated mice. Conclusion: The data presented in this report highlight the ability of E. coli derived ProGP-4 to expand large numbers of functional DC in the peripheral blood and lymphoid organs in vivo using a rodent model of hematopoiesis. E. coli derived chimeric receptor agonists such as ProGP-4 may enable further investigations of imnmnotherapeutic approaches to the treatment of diseases such as cancer and autoimmunity.",
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AU - Kahn, Larry E.

AU - Doshi, Parul

AU - McGarity, Kelly L.

AU - Yu, Mingfu

AU - Bono, Christine P.

AU - Lie, Wen Rong

AU - Rankin, Anne M.

AU - Smidt, Mary L.

AU - Streeter, Philip

AU - Klein, Barbara K.

AU - Welply, Joseph K.

AU - Woulfe, Susan L.

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N2 - Background: Progenipoietin-4 (ProGP-4) is an E. coli derived chimeric growth factor that activates the human Flt3 and G-CSF receptors. ProGP-4 possesses cross-species activity and treatment of mice with ProGP-4 results in increases in the number of WBC and Class II+/CD11c+ cells in both spleen and peripheral blood. Herein, we report morphologic, phenotypic and functional evaluation of Class II+/CD11c+ cells generated by in vivo administration of ProGP-4. Material/Methods: C57BL/6 mice were injected daily with ProGP for 7 to 18 days. Leukocytes from spleen and peripheral blood were analyzed by flow cytometry to enumerate and characterize changes in DC populations. Spleens from ProGP treated mice were evaluated by immunocytochemistry and enriched CD11c+ populations were functionally assessed in a mixed lymphocyte assay and in an antigen dependent CTL assay. Results: Administration of this dual receptor agonist to mice resulted in dose-dependent increases in the numbers of total white blood cells and Class II+/CD11c+ cells in spleen and peripheral blood. CD11c+ cells from ProGP-4 treated mice co-expressed DEC205 and also expressed CD80, CD86 and CD40, albeit at lower levels as compared to Class 11+/CD11c+ cells from untreated animals. Despite lower co-stimulatory molecule expression, ProGP-4-generated Class 11+/CD11c+ cells stimulated proliferation of allogeneic T cells and an antigen-specific T cell hybridoma as efficiently as bone marrow derived dendritic cells from untreated mice. Conclusion: The data presented in this report highlight the ability of E. coli derived ProGP-4 to expand large numbers of functional DC in the peripheral blood and lymphoid organs in vivo using a rodent model of hematopoiesis. E. coli derived chimeric receptor agonists such as ProGP-4 may enable further investigations of imnmnotherapeutic approaches to the treatment of diseases such as cancer and autoimmunity.

AB - Background: Progenipoietin-4 (ProGP-4) is an E. coli derived chimeric growth factor that activates the human Flt3 and G-CSF receptors. ProGP-4 possesses cross-species activity and treatment of mice with ProGP-4 results in increases in the number of WBC and Class II+/CD11c+ cells in both spleen and peripheral blood. Herein, we report morphologic, phenotypic and functional evaluation of Class II+/CD11c+ cells generated by in vivo administration of ProGP-4. Material/Methods: C57BL/6 mice were injected daily with ProGP for 7 to 18 days. Leukocytes from spleen and peripheral blood were analyzed by flow cytometry to enumerate and characterize changes in DC populations. Spleens from ProGP treated mice were evaluated by immunocytochemistry and enriched CD11c+ populations were functionally assessed in a mixed lymphocyte assay and in an antigen dependent CTL assay. Results: Administration of this dual receptor agonist to mice resulted in dose-dependent increases in the numbers of total white blood cells and Class II+/CD11c+ cells in spleen and peripheral blood. CD11c+ cells from ProGP-4 treated mice co-expressed DEC205 and also expressed CD80, CD86 and CD40, albeit at lower levels as compared to Class 11+/CD11c+ cells from untreated animals. Despite lower co-stimulatory molecule expression, ProGP-4-generated Class 11+/CD11c+ cells stimulated proliferation of allogeneic T cells and an antigen-specific T cell hybridoma as efficiently as bone marrow derived dendritic cells from untreated mice. Conclusion: The data presented in this report highlight the ability of E. coli derived ProGP-4 to expand large numbers of functional DC in the peripheral blood and lymphoid organs in vivo using a rodent model of hematopoiesis. E. coli derived chimeric receptor agonists such as ProGP-4 may enable further investigations of imnmnotherapeutic approaches to the treatment of diseases such as cancer and autoimmunity.

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