Murine T lymphocytes incapable of producing macrophage inhibitory protein-1α are impaired in causing graft-versus-host disease across a class I but not class II major histocompatibility complex barrier

Jonathan S. Serody, Donald N. Cook, Suzanne L. Kirby, Elizabeth Reap, Thomas C. Shea, Jeffrey A Frelinger

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The routine use of bone marrow transplantation is limited by the occurrence of acute and chronic graft-versus-host disease (GVHD). Current approaches to decreasing the occurrence of GVHD after allogeneic transplantation use T-cell depletion, use immunosuppressive agents, or block costimulatory molecule function. The role of proteins in the recruitment of alloreactive lymphocytes has not been well characterized. Chemokines are a large family of proteins that mediate recruitment of mononuclear cells in vitro and in vivo. To investigate the role of T-cell production of the chemokine macrophage inhibitory protein-1α (MIP-1α) in the occurrence of GVHD, splenocytes either from wild-type or from MIP-1α-/- mice were administered to class I (B6.C-H2bm1) and class II disparate mice (B6-C- H2bm12). The incidence and severity of GVHD was markedly reduced in bm1 mice receiving splenocytes from MIP-1α-/- mice as compared with mice receiving wild-type splenocytes. Bm1 mice receiving MIP-1α-/- splenocytes had significantly less weight loss and markedly reduced inflammatory responses in the lung and liver than mice receiving C57BL/6 splenocytes. Bm1 mice receiving MIP-1α-/- splenocytes had a markedly decreased production of antichromatin autoantibodies and impaired generation of bm1-specific T lymphocytes versus wild-type mice. However, MIP-1α-/- splenocytes easily induced GVHD when administered to bm12 mice. This data show that blockade of chemokine production or function may provide a new approach to the prevention or treatment of GVHD but that chemokines that recruit both CD4+ and CD8+ lymphocytes may need to be targeted.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalBlood
Volume93
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

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T-cells
Macrophages
Graft vs Host Disease
Major Histocompatibility Complex
Grafts
T-Lymphocytes
Chemokines
Proteins
Lymphocytes
Transplantation (surgical)
Homologous Transplantation
Immunosuppressive Agents
Bone Marrow Transplantation
Inbred C57BL Mouse
Liver
Autoantibodies
Weight Loss
Bone
Lung
Molecules

ASJC Scopus subject areas

  • Hematology

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Murine T lymphocytes incapable of producing macrophage inhibitory protein-1α are impaired in causing graft-versus-host disease across a class I but not class II major histocompatibility complex barrier. / Serody, Jonathan S.; Cook, Donald N.; Kirby, Suzanne L.; Reap, Elizabeth; Shea, Thomas C.; Frelinger, Jeffrey A.

In: Blood, Vol. 93, No. 1, 01.01.1999, p. 43-50.

Research output: Contribution to journalArticle

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abstract = "The routine use of bone marrow transplantation is limited by the occurrence of acute and chronic graft-versus-host disease (GVHD). Current approaches to decreasing the occurrence of GVHD after allogeneic transplantation use T-cell depletion, use immunosuppressive agents, or block costimulatory molecule function. The role of proteins in the recruitment of alloreactive lymphocytes has not been well characterized. Chemokines are a large family of proteins that mediate recruitment of mononuclear cells in vitro and in vivo. To investigate the role of T-cell production of the chemokine macrophage inhibitory protein-1α (MIP-1α) in the occurrence of GVHD, splenocytes either from wild-type or from MIP-1α-/- mice were administered to class I (B6.C-H2bm1) and class II disparate mice (B6-C- H2bm12). The incidence and severity of GVHD was markedly reduced in bm1 mice receiving splenocytes from MIP-1α-/- mice as compared with mice receiving wild-type splenocytes. Bm1 mice receiving MIP-1α-/- splenocytes had significantly less weight loss and markedly reduced inflammatory responses in the lung and liver than mice receiving C57BL/6 splenocytes. Bm1 mice receiving MIP-1α-/- splenocytes had a markedly decreased production of antichromatin autoantibodies and impaired generation of bm1-specific T lymphocytes versus wild-type mice. However, MIP-1α-/- splenocytes easily induced GVHD when administered to bm12 mice. This data show that blockade of chemokine production or function may provide a new approach to the prevention or treatment of GVHD but that chemokines that recruit both CD4+ and CD8+ lymphocytes may need to be targeted.",
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