Abstract
CD4+latency-associated peptide (LAP)+ T cells are a newly discovered T cell subset with suppressive function on immune responses. In this study, we investigate the role of CD4+LAP+ T cells on mice corneal allograft survival by down-regulating their expression using anti-LAP mAb. We show that a blockage of LAP leads to a decrease in the percentage of T cells expressing CD4+Foxp3+, CD4+GARP+, CD4+LAP+ and CD4+IL-10+ in the lymph nodes and spleens of mice undergoing orthotopic penetrating transplantation of corneal allograft, without affecting corneal graft survival. In addition, higher percentages of CD4+IFN-γ+ and CD4+IL-17A+ T cells in the lymph nodes and spleens, as well as TNF, IFN-γ, IL-17A and IL-6 levels in the aqueous humor, significantly increase in mice with rejected corneal grafts. The expression of TGF-β1 decreases in corneal grafts during corneal rejection period. It is therefore possible that anti-LAP mAb can down-regulate the regulatory T cell subsets with its immunosuppressive effects. The rejection of corneal grafts seems to mainly be associated with the up-regulation of Th1 and Th17 cell subsets in peripheral lymph nodes.
Highlights
Histopathological staining of the grafts 21 days after corneal transplantation showed normal corneal thickness and few inflammatory cells infiltrating the edge of the recipient bed in the non-rejectors of the anti-latency-associated peptide (LAP) treated mice, similar to what was seen in the syngeneic grafts
Compared with non-rejected allograft mice, the mRNA expression of TGF-β1 in the rejectors of the isotype IgG1 group significantly decreased at the third and fourth weeks after surgery (Pw3 < 0.001, Pw4 = 0.002). This present study is the first to note that the percentages of CD4+LAP+ T cells and CD4+glycoprotein A repetitions predominant (GARP)+ T cells in the lymph nodes and spleens of mice after corneal transplantation are significantly lower in rejected corneas
LAP expression in our study was consistent with GARP expression on CD4+ T cells, supporting previous studies in a mouse model suggesting that the surface LAP is GARP-anchored in CD4+ T cells[20]
Summary
These cells share some common features including expression of Foxp[3] and secretion of inhibitory cytokine IL-10 and TGF-β8. Foxp[3] expression, was found in activated effector T cells (Tresp)[9]. Stockis et al found that glycoprotein A repetitions predominant (GARP) and latency-associated peptide (LAP) were expressed on the surface of nTregs simultaneously, but not on Tresp[10]. GARP and LAP are considered to be new specific markers of activated Tregs. LAP and TGF-β form inactive complexes on the surfaces of CD4+CD25+ T cells, known as latent TGF-β complexes[11]. GARP is a latent TGF-β binding protein that functions by regulating the bioavailability and activation of TGF-β, mediating CD4+CD25+ T cells’ suppressive functions[12,13]. We used anti-LAP mAb to assess whether it would aggravate corneal immune rejection response
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
