A role for natural killer T cells and CD1d molecules in counteracting suppression of hematopoiesis in mice induced by infection with murine cytomegalovirus

Hal Broxmeyer, Alexander Dent, Scott Cooper, Giao Hangoc, Zheng Yu Wang, Wenjun Du, Jacquelyn Gervay-Haque, Venkataraman Sriram, Gourapura J. Renukaradhya, Randy Brutkiewicz

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Infection of immunocompromised patients with cytomegalovirus (CMV), such as that occurring in patients undergoing hematopoietic stem cell transplantation, is a serious clinical problem. CMV infection has been reported to suppress hematopoiesis. In immunocompetent hosts CMV is controlled initially by the innate immune system, with CD1d molecules and natural killer T (NKT) cells playing a role in the antiviral immune response in several model systems. We hypothesized that CD1d and NKT cells are involved in protection of the hematopoietic modulating effects of CMV, and that adoptive transfer of NKT cells would protect against these infection-induced effects. Methods: To address our hypothesis, we used a murine CMV (MCMV) infection model in CD1d-/-, Jα18-/-, and wild-type (WT) control mice of two different genetic strains each. Results: Infection with MCMV was associated with significant suppression of absolute numbers and cell cycling status of myeloid progenitor cells (CFU-GM, BFU-E, CFU-GEMM) in the marrow and spleen, especially in CD1d-/- (lack both CD1d and NKT cells), and Jα18-/- (express CD1d but lack NKT cells) mice. Adoptive transfer of NKT cells into WT and Jα18-/- mice shortly before infection with MCMV counteracted myelosuppression. Conclusions: The results implicate NKT cells, and also likely CD1d, in protection of progenitor cells from MCMV-induced suppression and suggest that NKT cells may be of value in an adoptive transfer setting to treat CMV-induced perturbations of hematopoiesis in immunocompromised individuals. However, further studies are required to better understand the full consequences of adoptive transfer in these settings.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalExperimental Hematology
Volume35
Issue number4 SUPPL.
DOIs
StatePublished - Apr 2007

Fingerprint

CD1d Antigen
Muromegalovirus
Natural Killer T-Cells
Hematopoiesis
Adoptive Transfer
Infection
Cytomegalovirus
Myeloid Progenitor Cells
Cytomegalovirus Infections
Erythroid Precursor Cells
Hematopoietic Stem Cell Transplantation
Immunocompromised Host
Antiviral Agents
Immune System
Stem Cells
Spleen
Cell Count
Bone Marrow

ASJC Scopus subject areas

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

Cite this

A role for natural killer T cells and CD1d molecules in counteracting suppression of hematopoiesis in mice induced by infection with murine cytomegalovirus. / Broxmeyer, Hal; Dent, Alexander; Cooper, Scott; Hangoc, Giao; Wang, Zheng Yu; Du, Wenjun; Gervay-Haque, Jacquelyn; Sriram, Venkataraman; Renukaradhya, Gourapura J.; Brutkiewicz, Randy.

In: Experimental Hematology, Vol. 35, No. 4 SUPPL., 04.2007, p. 87-93.

Research output: Contribution to journalArticle

Broxmeyer, Hal ; Dent, Alexander ; Cooper, Scott ; Hangoc, Giao ; Wang, Zheng Yu ; Du, Wenjun ; Gervay-Haque, Jacquelyn ; Sriram, Venkataraman ; Renukaradhya, Gourapura J. ; Brutkiewicz, Randy. / A role for natural killer T cells and CD1d molecules in counteracting suppression of hematopoiesis in mice induced by infection with murine cytomegalovirus. In: Experimental Hematology. 2007 ; Vol. 35, No. 4 SUPPL. pp. 87-93.
@article{08dba477d3c54e91ac447168fa51f06c,
title = "A role for natural killer T cells and CD1d molecules in counteracting suppression of hematopoiesis in mice induced by infection with murine cytomegalovirus",
abstract = "Objective: Infection of immunocompromised patients with cytomegalovirus (CMV), such as that occurring in patients undergoing hematopoietic stem cell transplantation, is a serious clinical problem. CMV infection has been reported to suppress hematopoiesis. In immunocompetent hosts CMV is controlled initially by the innate immune system, with CD1d molecules and natural killer T (NKT) cells playing a role in the antiviral immune response in several model systems. We hypothesized that CD1d and NKT cells are involved in protection of the hematopoietic modulating effects of CMV, and that adoptive transfer of NKT cells would protect against these infection-induced effects. Methods: To address our hypothesis, we used a murine CMV (MCMV) infection model in CD1d-/-, Jα18-/-, and wild-type (WT) control mice of two different genetic strains each. Results: Infection with MCMV was associated with significant suppression of absolute numbers and cell cycling status of myeloid progenitor cells (CFU-GM, BFU-E, CFU-GEMM) in the marrow and spleen, especially in CD1d-/- (lack both CD1d and NKT cells), and Jα18-/- (express CD1d but lack NKT cells) mice. Adoptive transfer of NKT cells into WT and Jα18-/- mice shortly before infection with MCMV counteracted myelosuppression. Conclusions: The results implicate NKT cells, and also likely CD1d, in protection of progenitor cells from MCMV-induced suppression and suggest that NKT cells may be of value in an adoptive transfer setting to treat CMV-induced perturbations of hematopoiesis in immunocompromised individuals. However, further studies are required to better understand the full consequences of adoptive transfer in these settings.",
author = "Hal Broxmeyer and Alexander Dent and Scott Cooper and Giao Hangoc and Wang, {Zheng Yu} and Wenjun Du and Jacquelyn Gervay-Haque and Venkataraman Sriram and Renukaradhya, {Gourapura J.} and Randy Brutkiewicz",
year = "2007",
month = "4",
doi = "10.1016/j.exphem.2007.01.015",
language = "English",
volume = "35",
pages = "87--93",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "4 SUPPL.",

}

TY - JOUR

T1 - A role for natural killer T cells and CD1d molecules in counteracting suppression of hematopoiesis in mice induced by infection with murine cytomegalovirus

AU - Broxmeyer, Hal

AU - Dent, Alexander

AU - Cooper, Scott

AU - Hangoc, Giao

AU - Wang, Zheng Yu

AU - Du, Wenjun

AU - Gervay-Haque, Jacquelyn

AU - Sriram, Venkataraman

AU - Renukaradhya, Gourapura J.

AU - Brutkiewicz, Randy

PY - 2007/4

Y1 - 2007/4

N2 - Objective: Infection of immunocompromised patients with cytomegalovirus (CMV), such as that occurring in patients undergoing hematopoietic stem cell transplantation, is a serious clinical problem. CMV infection has been reported to suppress hematopoiesis. In immunocompetent hosts CMV is controlled initially by the innate immune system, with CD1d molecules and natural killer T (NKT) cells playing a role in the antiviral immune response in several model systems. We hypothesized that CD1d and NKT cells are involved in protection of the hematopoietic modulating effects of CMV, and that adoptive transfer of NKT cells would protect against these infection-induced effects. Methods: To address our hypothesis, we used a murine CMV (MCMV) infection model in CD1d-/-, Jα18-/-, and wild-type (WT) control mice of two different genetic strains each. Results: Infection with MCMV was associated with significant suppression of absolute numbers and cell cycling status of myeloid progenitor cells (CFU-GM, BFU-E, CFU-GEMM) in the marrow and spleen, especially in CD1d-/- (lack both CD1d and NKT cells), and Jα18-/- (express CD1d but lack NKT cells) mice. Adoptive transfer of NKT cells into WT and Jα18-/- mice shortly before infection with MCMV counteracted myelosuppression. Conclusions: The results implicate NKT cells, and also likely CD1d, in protection of progenitor cells from MCMV-induced suppression and suggest that NKT cells may be of value in an adoptive transfer setting to treat CMV-induced perturbations of hematopoiesis in immunocompromised individuals. However, further studies are required to better understand the full consequences of adoptive transfer in these settings.

AB - Objective: Infection of immunocompromised patients with cytomegalovirus (CMV), such as that occurring in patients undergoing hematopoietic stem cell transplantation, is a serious clinical problem. CMV infection has been reported to suppress hematopoiesis. In immunocompetent hosts CMV is controlled initially by the innate immune system, with CD1d molecules and natural killer T (NKT) cells playing a role in the antiviral immune response in several model systems. We hypothesized that CD1d and NKT cells are involved in protection of the hematopoietic modulating effects of CMV, and that adoptive transfer of NKT cells would protect against these infection-induced effects. Methods: To address our hypothesis, we used a murine CMV (MCMV) infection model in CD1d-/-, Jα18-/-, and wild-type (WT) control mice of two different genetic strains each. Results: Infection with MCMV was associated with significant suppression of absolute numbers and cell cycling status of myeloid progenitor cells (CFU-GM, BFU-E, CFU-GEMM) in the marrow and spleen, especially in CD1d-/- (lack both CD1d and NKT cells), and Jα18-/- (express CD1d but lack NKT cells) mice. Adoptive transfer of NKT cells into WT and Jα18-/- mice shortly before infection with MCMV counteracted myelosuppression. Conclusions: The results implicate NKT cells, and also likely CD1d, in protection of progenitor cells from MCMV-induced suppression and suggest that NKT cells may be of value in an adoptive transfer setting to treat CMV-induced perturbations of hematopoiesis in immunocompromised individuals. However, further studies are required to better understand the full consequences of adoptive transfer in these settings.

UR - http://www.scopus.com/inward/record.url?scp=33947279009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947279009&partnerID=8YFLogxK

U2 - 10.1016/j.exphem.2007.01.015

DO - 10.1016/j.exphem.2007.01.015

M3 - Article

C2 - 17379092

AN - SCOPUS:33947279009

VL - 35

SP - 87

EP - 93

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

IS - 4 SUPPL.

ER -