Viral IL-10-induced immunosuppression requires Th2 cytokines and impairs APC function within the allograft.

TitleViral IL-10-induced immunosuppression requires Th2 cytokines and impairs APC function within the allograft.
Publication TypeJournal Article
Year of Publication2001
AuthorsQin L, Ding Y, Tahara H, Bromberg JS
JournalJ Immunol
Date Published2001 Feb 15
KeywordsAnimals, Antibodies, Monoclonal, Antigen Presentation, Antigen-Presenting Cells, B-Lymphocyte Subsets, CD4 Antigens, CD4-Positive T-Lymphocytes, Cell Movement, Cytokines, Female, Gene Transfer Techniques, Graft Enhancement, Immunologic, Graft Survival, Heart Transplantation, Immune Tolerance, Immunophenotyping, Immunosuppressive Agents, Injections, Intralesional, Injections, Intravenous, Interferon-gamma, Interleukin-10, Interleukin-4, Isoantigens, Leukocyte Count, Lymphocyte Culture Test, Mixed, Macrophages, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, T-Lymphocyte Subsets, Th2 Cells, Transplantation, Homologous, Viral Proteins

Previous reports demonstrated that retroviral mediated gene transfer of viral IL-10 (vIL-10) prolongs allograft survival by decreasing donor-specific cytotoxic T lymphocyte precursor (CTLp) and IL-2-secreting helper T lymphocyte precursor (HTLp) frequency within graft-infiltrating cells (GIC). This report now shows that vIL-10 efficacy is dependent on CD4(+) T cells, suggesting that immunosuppression may involve a switch from a Th1 to a Th2 alloresponse. In support of this, anti-IL-4 or anti-murine IL-10 (anti-mIL-10) mAbs, but not anti-IFN-gamma mAb, administered at the time of vIL-10 gene transfer prevents enhanced graft survival. Because Th switching involves APC function, GIC were examined for their ability to present alloantigen. GIC from vIL-10-treated grafts were shown to be mostly of recipient (CBA) origin, yet were unable to elicit alloproliferative responses from donor type (C57BL/6) or third party (BALB/c) responders. The inability of vIL-10-treated GIC to stimulate the MLR was not due to the generation of negative regulatory cells or the production of immunosuppressive cytokines such as IL-4, mIL-10, or TGFbeta. Using fractionated GIC subpopulations, the number of recipient type cells in the allografts was modestly reduced by vIL-10 gene transfer, while maintaining both APC phenotype and alloantigen presenting function. Conversely, after vIL-10 gene transfer, donor type GIC were unable to participate in direct alloantigen presentation. Therefore, local immunosuppression induced by vIL-10 gene transfer is CD4 T cell and IL-4 and mIL-10 dependent, and impairs direct alloantigen presentation through an alteration of donor type APC function.

Alternate JournalJ Immunol
PubMed ID11160297
Grant ListAI 32655 / AI / NIAID NIH HHS / United States
P60-AR20557 / AR / NIAMS NIH HHS / United States
Related Faculty: 
Lihui Qin, M.D., Ph.D.

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