Interleukin-5 (IL-5) Therapy Prevents Allograft Rejection by Promoting CD4+CD25+ Ts2 Regulatory Cells That Are Antigen-Specific and Express IL-5 Receptor
| Autor: | Catherine M. Robinson, Nirupama D. Verma, Prateek Rakesh, Giang T. Tran, Suzanne Hodgkinson, Chuanmin Wang, Bruce M. Hall, Alexandra F. Sharland, R. M. R. Hall, Paul L. Wilcox |
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| Rok vydání: | 2021 |
| Předmět: |
Messenger RNA
allograft rejection business.industry T regulatory cells Immunology FOXP3 hemic and immune systems chemical and pharmacologic phenomena RC581-607 cytokines Transplantation transplant tolerance chronic rejection Antigen specific Immunology and Allergy Medicine interleukin-5 IL-2 receptor Immunologic diseases. Allergy Receptor business Interleukin 5 IRF4 |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.714838 |
| Popis: | CD4+CD25+Foxp3+T cell population is heterogenous and contains three major sub-groups. First, thymus derived T regulatory cells (tTreg) that are naïve/resting. Second, activated/memory Treg that are produced by activation of tTreg by antigen and cytokines. Third, effector lineage CD4+CD25+T cells generated from CD4+CD25-T cells’ activation by antigen to transiently express CD25 and Foxp3. We have shown that freshly isolated CD4+CD25+T cells are activated by specific alloantigen and IL-4, not IL-2, to Ts2 cells that express the IL-5 receptor alpha. Ts2 cells are more potent than naïve/resting tTreg in suppressing specific alloimmunity. Here, we showed rIL-5 promoted further activation of Ts2 cells to Th2-like Treg, that expressedfoxp3, irf4, gata3andil5. In vivo, we studied the effects of rIL-5 treatment on Lewis heart allograft survival in F344 rats. Host CD4+CD25+T cells were assessed by FACS, in mixed lymphocyte culture and by RT-PCR to examine mRNA of Ts2 or Th2-like Treg markers. rIL-5 treatment given 7 days after transplantation reduced the severity of rejection and all grafts survived ≥60d whereas sham treated rats fully rejected by day 31 (p+CD25+cells expressed moreIl5raand responded to specific donor Lewis but not self. Enriched CD4+CD25+cells from rIL-5 treated rats with allografts surviving >60 days proliferated to specific donor only when rIL-5 was present and did not proliferate to self or third party. These cells had more mRNA for molecules expressed by Th2-like Treg including Irf4, gata3andIl5.These findings were consistent with IL-5 treatment preventing rejection by activation of Ts2 cells and Th2-like Treg. |
| Databáze: | OpenAIRE |
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