Tolerance induction by anti-CD2 plus anti-CD3 monoclonal antibodies: evidence for an IL-4 requirement.

TitleTolerance induction by anti-CD2 plus anti-CD3 monoclonal antibodies: evidence for an IL-4 requirement.
Publication TypeJournal Article
Year of Publication1998
AuthorsPunch JD, Tono T, Qin L, Bishop DK, Bromberg JS
JournalJ Immunol
Date Published1998 Aug 01
KeywordsAnimals, Antibodies, Monoclonal, CD2 Antigens, CD3 Complex, Cytokines, Drug Synergism, Female, Graft Survival, Heart Transplantation, Immune Tolerance, Injections, Intravenous, Interleukin-10, Interleukin-4, Isoantibodies, Isoantigens, Lymphocyte Culture Test, Mixed, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Th1 Cells

Anti-CD2 mAb plus anti-CD3 mAb induce alloantigen specific tolerance. We sought to determine whether Th2 cytokines are involved in the induction of tolerance in this model. Addition of anti-IL-4 mAb or anti-IL-10 mAb to anti-CD2 plus anti-CD3 treatment abrogated tolerance and resulted in graft survivals of 26+/-4 and 25+/-5 days, respectively. Splenocytes from the anti-IL-4 mAb and anti-IL-10 groups had greater proliferation in response to alloantigen than either tolerant or naive groups. Cytokine analysis of MLR supernatants showed increased IL-10 in the tolerant group and increased IFN-gamma in the anti-IL-4 mAb treated group. Donor-specific alloantibody responses in untreated immune animals had a predominantly Th1 (IgG2a) alloantibody response, while the tolerogenic regimen reduced the ratio of IgG2a:IgG1 titers. The addition of anti-IL-4 mAb to the tolerogenic regimen partly restored the Th1-related IgG2a response. Tolerance did not develop in IL-4 knockout animals treated with anti-CD2 plus anti-CD3 (mean graft survival, 27+/-5 days). Restoration of IL-4 to IL-4 knockout animals by gene transfer with plasmid DNA resulted in prolongation of survival to 46+/-7 days, while adoptive transfer of wild-type splenocytes into IL-4 knockout recipients resulted in indefinite graft survival (>60 days) and indefinite survival of second donor-type grafts. IL-10 gene transfer to IL-4 knockout recipients did not prolong graft survival (28+/-4). These results demonstrate that tolerance in this model is mediated at least in part by Th2-type cells that secrete IL-4, promote IL-10 and IgG1 production, and inhibit alloantigen reactivity.

Alternate JournalJ Immunol
PubMed ID9686574
Grant ListAI32655 / AI / NIAID NIH HHS / United States
AI41428 / 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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