Title | Viral IL-10-induced immunosuppression requires Th2 cytokines and impairs APC function within the allograft. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Qin L, Ding Y, Tahara H, Bromberg JS |
Journal | J Immunol |
Volume | 166 |
Issue | 4 |
Pagination | 2385-93 |
Date Published | 2001 Feb 15 |
ISSN | 0022-1767 |
Keywords | Animals, 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 |
Abstract | 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. |
DOI | 10.4049/jimmunol.166.4.2385 |
Alternate Journal | J Immunol |
PubMed ID | 11160297 |
Grant List | AI 32655 / AI / NIAID NIH HHS / United States P60-AR20557 / AR / NIAMS NIH HHS / United States |
Related Faculty:
Lihui Qin, M.D., Ph.D.