Abstract
The direct interaction between antigen specific CD8(+) CD28(-) T suppressor cells (T(S)) with dendritic cells (DC) results in the tolerization of DC by inducing the upregulation of immunologlobulin like transcript 3 (ILT3) and ILT4. We show here that such tolerogenic DC anergize alloreactive CD4(+) CD45RO(+) CD25(+) T cells converting them into regulatory T cells (T(R)), which in turn, continue the cascade of suppression by tolerizing other DC. Interleukin 10 (IL-10) and interferon-alpha (IFN-alpha) also induce ILT3 and ILT4 upregulation in DC, rendering them tolerogenic. This implies a common mechanism of DC-mediated suppression. This finding and the observation that in organ allograft recipients quiescence is associated with the presence in the circulation of donor-specific T(S) and T(R) emphasize the importance of the cross talk between tolerogenic DC and T cells in suppression of the immune response.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / transplantation
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Cholecalciferol / pharmacology
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Cytokines / pharmacology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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HLA-DR Antigens / metabolism
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Humans
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Interleukin-3 / metabolism
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Interleukin-4 / metabolism
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Leukocyte Common Antigens / metabolism
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Membrane Glycoproteins
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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Receptors, Interleukin-2 / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / transplantation
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / transplantation
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Transplantation Tolerance*
Substances
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Cytokines
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HLA-DR Antigens
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Interleukin-3
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LILRB2 protein, human
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LILRB4 protein, human
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Immunologic
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Receptors, Interleukin-2
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Cholecalciferol
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Interleukin-4
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Leukocyte Common Antigens