Evidence That Ifn-7 Is Responsible for Natural Suppressor Activity in GVHD Spleen and Normal Bone Marrow

Holda, James H.; Maier, Tom; Claman, Henry N.

doi:10.1097/00007890-198804000-00021

Cited by 30 publications

(12 citation statements)

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“…However, neutralization of IFN␥ resulted in dysregulation of the inflammatory response and severe interstitial pneumonitis in mice undergoing GVHD. Although IFN␥ is associated with immunosuppression after BMT (12)(13)(14)(15), it is clear from the studies presented here that the presence of IFN␥ after allogeneic BMT is beneficial in controlling P. carinii-driven inflammation in the lungs.…”

Section: Discussionmentioning

confidence: 90%

“…Furthermore, IFN ␥ , a cytokine secreted by Th1 cells (10), has been shown to be secreted by alloreactive T cells in a minor Mls antigen model of murine acute GVHD (11). IFN ␥ has been implicated in immunosuppression characterized by the ability of cells from mice with GVHD to suppress both in vitro activation of normal T cells (12)(13)(14) and bone marrow B cell development (15). Neutralization of IFN ␥ either in vivo or in vitro has been shown to remove immunosuppression associated with alloreactive cells (14,15).…”

Section: Introductionmentioning

confidence: 99%

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Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice.

Garvy

Gigliotti²,

Harmsen³

1997

J. Clin. Invest.

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The role of IFN ␥ in the development of infection-driven interstitial pneumonitis in a model of murine graft-versushost disease was investigated. Mice were given either syngeneic or allogeneic bone marrow transplants along with lung Pneumocystis carinii infections and were treated with either control mAb or anti-IFN ␥ mAb. At day 21 after transplant, lung weights were elevated nearly twofold in all groups. By day 41, mice in all groups had cleared the P. carinii but only the mice given allogeneic transplants and anti-IFN ␥ had increased lung weights.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice.

Garvy

Gigliotti²,

Harmsen³

1997

J. Clin. Invest.

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“…In most instances this suppressor activity is nonconstitutive, but is induced upon proper cell activation (19). In this regard T cell signals have been described to play a critical role (20,21). Previously, we have shown that bone marrow-derived natural suppressor activity is mediated by NO (22), which is produced in large quantities by early myeloid cells following IFN-␥ plus CD40 stimulation (23).…”

Section: Yclophosphamide (Cy)mentioning

confidence: 99%

Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism

Peláez

Campillo

López-Asenjo

et al. 2001

The Journal of Immunology

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Adoptive immunotherapy with cyclophosphamide (Cy) increases the host resistance against tumor growth. The precise mechanism(s) by which this therapy enhances tumor suppression is unclear. Cy induces the development of early myeloid cells that may be strongly antiproliferative through NO production. These cells are similar to the natural suppressor cells found in normal bone marrow with a potential antitumor effect. Here we have addressed whether the development of NO-producing cells may be involved in this tumor resistance in Cy-treated mice. The results show a synergism between Cy treatment and tumor-specific lymphocytes transferred systemically (i.v.) or locally (Winn’s assay) that results in a strong tumor suppression. Inhibition of NO production by NG-monomethyl-l-arginine at the site of tumor inoculation results in a loss of the protection achieved by the combined therapy. Cy-treated mice develop splenic early myeloid (CD11b, Gr-1, CD31 (ER-MP12), ER-MP20, ER-MP54) cells producing large amounts of NO upon T cell-derived signals (IFN-γ plus CD40 ligation) able to inhibit tumor cell growth in vitro. Early myeloid cells (ER-MP54+) and cells expressing inducible NO synthase are increased at the site of tumor challenge in mice treated with the combined therapy, but not in those treated with Cy or immune cell transfer alone. Thus, Cy induces the expansion of early myeloid cells, inhibiting tumor cell growth by a mechanism involving NO. Both the recruitment and the activation of these myeloid cells at the site of tumor challenge appear to be dependent on the presence of tumor-specific lymphocytes.

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“…In contrast to studies showing an important role for IFN-␥ in the induction of GVHD (16)(17)(18)(19)(20), exogenous IFN-␥ has been previously shown to inhibit GVHD (21). Also, despite studies suggesting an important role for IFN-␥ in the pathogenesis of GVHD-associated immunodeficiency (22)(23)(24)(25), IFN-␥ has been shown to improve immunocompetence (26) and protect from infections (27) in allogeneic BMT recipients. We have recently reported that IL-12 treatment has a biphasic effect on serum IFN-␥ levels in murine GVHD models, leading to an early increase on days 2 and 3, followed by an almost complete inhibition on day 4, when serum IFN-␥ levels peak in untreated GVHD controls (8).…”

Section: Introductionmentioning

confidence: 99%

Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12.

Yang¹,

Dey²,

Sergio³

et al. 1998

J. Clin. Invest.

169

145

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Evidence That Ifn-7 Is Responsible for Natural Suppressor Activity in GVHD Spleen and Normal Bone Marrow

Cited by 30 publications

References 0 publications

Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice.

Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice.

Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism

Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12.

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