Intrathymic maturation of CD4+ T-lymphocytes in an MHC class II deficient transplant model

Human gamma interferon (HuIFN gamma) was assessed for its capacity to enhance release of granulocyte-macrophage colony stimulating factors (GM-CSF) from human peripheral blood monocytes. Natural HuIFN gamma (2 X 10(7) NIH reference units per milligram) at concentrations as low as 0.01 U/mL to 10 U/mL reproducibly enhanced release of GM-CSF. This enhancement was detected when T lymphocytes were depleted from monocyte preparations and when T lymphocytes and monocytes were depleted from populations of human bone marrow cells stimulated by monocyte- conditioned media to form colonies and clusters. T lymphocytes alone or in the presence of HuIFN gamma did not release GM-CSF. The enhancing activity of HuIFN gamma was removed by preincubating HuIFN gamma with neutralizing concentrations of monoclonal anti-HuIFN gamma, and recombinant HuIFN gamma mimicked the effects of natural HuIFN gamma, suggesting that the effects were due to HuIFN gamma itself. HuIFN gamma suppression of the release of inhibitory activity from monocytes was ruled out as a reason for the noted enhancing activity of HuIFN gamma. The enhancing activity of HuIFN gamma was confined to the MHC class II antigen-positive population of monocytes. Removal of these cells with monoclonal antibody plus complement (c') ablated the enhancing activity, high concentrations of certain monoclonal antibodies in the absence of c' blocked the enhancing activity and, when monocytes were sorted into MHC class II antigen-positive and -negative cells by fluorescence-activated cell sorting, it was only the positive cell fraction that responded to the enhancing activity of HuIFN gamma.

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Increased numbers and suppressive activity of regulatory CD25+CD4+ T lymphocytes in the absence of CD4 engagement by MHC class II molecules

Cellular Immunology ◽

10.1016/j.cellimm.2013.05.002 ◽

2013 ◽

Vol 282 (2) ◽

pp. 117-128 ◽

Cited By ~ 2

Author(s):

Xiaoli Shen ◽

Chun Niu ◽

Rolf König

Keyword(s):

T Lymphocytes ◽

Mhc Class Ii ◽

Class Ii ◽

Suppressive Activity ◽

Mhc Class Ii Molecules

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Specificity of Effector T Lymphocytes in Autologous Graft-Versus-Host Disease: Role of the Major Histocompatibility Complex Class II Invariant Chain Peptide

Blood ◽

10.1182/blood.v89.6.2203 ◽

1997 ◽

Vol 89 (6) ◽

pp. 2203-2209 ◽

Cited By ~ 55

Author(s):

Allan D. Hess ◽

Emilie C. Bright ◽

Christopher Thoburn ◽

Georgia B. Vogelsang ◽

Richard J. Jones ◽

...

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Lymphocytes ◽

Mhc Class Ii ◽

Class Ii ◽

Effector T Cells ◽

Invariant Chain ◽

Target Cells ◽

Graft Versus Host ◽

Histocompatibility Complex

Abstract Administration of the immunosuppressive drug cyclosporine after autologous bone marrow transplantation induces a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome termed autologous GVHD has significant antitumor activity. Associated with autologous GVHD is the development of T lymphocytes that recognize major histocompatibility complex (MHC) class II determinants, including self. The present studies attempted to characterize and define the molecular specificity of the effector T lymphocytes in autologous GVHD induced in patients with metastatic breast cancer. The results suggest that the effector cells associated with human autologous GVHD are CD8+ T lymphocytes expressing the α/β T-cell receptor. Additional studies show that the effector T cells recognize MHC class II antigens in association with a peptide from the invariant chain (CLIP). Pretreatment of autologous lymphoblast target cells with anti-CLIP antibody completely blocked lysis mediated by autologous GVHD effector T cells. On the other hand, force loading this peptide markedly enhanced the susceptibility of the target cells to recognition by the autoreactive T cells. The recognition of the MHC class II CLIP complex may account for the novel specificity of the effector T cells associated with human autologous GVHD. Moreover, identification of the target peptide may allow for the development of novel immunotherapeutic strategies to enhance the antitumor efficacy of autologous GVHD.

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