Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non- Hodgkin's lymphoma patients

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Abstract

Objective. In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. Materials and Methods. We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. Results. Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-γ and tumor necrosis factor-α were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-γ were decreased significantly on day 365 compared with pretransplant levels. Conclusion. The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine. (C) 2000 International Society for Experimental Hematology.

Original languageEnglish (US)
Pages (from-to)499-507
Number of pages9
JournalExperimental Hematology
Volume28
Issue number5
DOIs
StatePublished - May 1 2000

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Peripheral Blood Stem Cell Transplantation
Non-Hodgkin's Lymphoma
Cytokines
Gene Expression
Messenger RNA
Drug Therapy
Interleukin-10
Interferons
Interleukin-2
Monokines
T-Lymphocytes
Interleukin-4
Blood Cells
Tumor Necrosis Factor-alpha
Transplantation
Peripheral Blood Stem Cells
Tissue Donors
Phenotype

Keywords

  • Cytokines
  • Gene expression
  • Immune reconstitution
  • NHL
  • Stem cell transplantation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

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title = "Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non- Hodgkin's lymphoma patients",
abstract = "Objective. In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. Materials and Methods. We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. Results. Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-γ and tumor necrosis factor-α were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-γ were decreased significantly on day 365 compared with pretransplant levels. Conclusion. The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine. (C) 2000 International Society for Experimental Hematology.",
keywords = "Cytokines, Gene expression, Immune reconstitution, NHL, Stem cell transplantation",
author = "Singh, {Rakesh K} and Varney, {Michelle L.} and Kazuhiko Ino and Vose, {Julie Marie} and Bierman, {Philip Jay} and Talmadge, {James E}",
year = "2000",
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T1 - Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non- Hodgkin's lymphoma patients

AU - Singh, Rakesh K

AU - Varney, Michelle L.

AU - Ino, Kazuhiko

AU - Vose, Julie Marie

AU - Bierman, Philip Jay

AU - Talmadge, James E

PY - 2000/5/1

Y1 - 2000/5/1

N2 - Objective. In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. Materials and Methods. We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. Results. Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-γ and tumor necrosis factor-α were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-γ were decreased significantly on day 365 compared with pretransplant levels. Conclusion. The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine. (C) 2000 International Society for Experimental Hematology.

AB - Objective. In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. Materials and Methods. We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. Results. Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-γ and tumor necrosis factor-α were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-γ were decreased significantly on day 365 compared with pretransplant levels. Conclusion. The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine. (C) 2000 International Society for Experimental Hematology.

KW - Cytokines

KW - Gene expression

KW - Immune reconstitution

KW - NHL

KW - Stem cell transplantation

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