MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the post-transcriptional expression of target genes and are important regulators in many biologic processes including innate and adaptive immune responses. Previous studies demonstrated that miR-182 was significantly increased in the lymphocytes that infiltrate rejecting allografts. Here, we transplanted BALB/c hearts into groups (n=4) of B6.129S-H2dlAb1-Ea (MHC II and CD4+ T cell deficient), B6.129S2-Tap1tm1Arp (MHC I and CD8+ T cell deficient) and wild-type (WT) C57BL/6 recipients and quantitated miR-182 levels by quantitative RT-PCR. MiR-182 was significantly decreased in the graft infiltrating cells and PBMC of B6.129S-H2dlAb1-Ea recipients of allografts as compared to WT recipients. In contrast, miR-182 levels was similar in the B6.129S2-Tap1tm1Arp recipients as compared to WT recipients strongly supporting that CD4+ T cells are the cellular source of miR-182 during allograft rejection. To determine if the absence of miR-182 could prolong graft survival we transplanted BALB/c hearts into WT and miR-182 knockout (KO) mice and assessed graft survival. There was a modest, yet significant (6.4 days WT vs. 8.2 days KO, P<0.01) increase in survival in the absence of miR-182. Based on our finding that CD4+ T cells are the source of miR-182 we hypothesized that blockade of costimulation in the absence of miR-182 may prolong graft survival. We treated WT (n=5) and miR-182 KO (n=8) recipients of BALB/c hearts with a low dose of CTLA4-Ig (Abatacept, 0.5 mg on day 0, 0.25 mg on days 2, 4, and 6). CTLA4-Ig alone prolongs graft survival, with a dramatic and significant doubling of graft survival in the absence of miR-182 (31.5 days WT vs. 60 days KO, P<0.01). Taken together our results indicate an important role for miR-182 in the CD4+ T cell response to alloantigen and suggest that therapeutics targeting specific miRNAs may prove beneficial in transplantation.
To cite this abstract in AMA style:Wei L, Qu X, Martinez O, Krams S. Absence of the MicroRNA miR-182 in CD4+T Cells Prolongs Allograft Survival [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/absence-of-the-microrna-mir-182-in-cd4t-cells-prolongs-allograft-survival/. Accessed June 13, 2021.
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