The effect of CTLA4-Ig on fibrotic progression in a murine model of chronic lung allograft dysfunction.

Co-stimulatory blockade has emerged as a promising strategy for preventing acute and chronic rejection in solid organ transplantation. This study investigates the efficacy of cytotoxic T-lymphocyte-associated protein-4-Ig (CTLA4-Ig), a T-cell co-stimulation blocker, in mitigating chronic lung allograft dysfunction (CLAD). Using a murine CLAD model, we demonstrated that CTLA4-Ig treatment significantly reduced fibrotic progression and cellular rejection when initiated immediately after transplantation compared to IgG1 Fc-isotype. CTLA4-Ig treatment resulted in a decreased number of intragraft CD3⁺ T cells, whereas B cell numbers and the CD4⁺/CD8⁺ ratio in the grafts remained unaffected. In contrast, when administered after the onset of acute rejection, CTLA4-Ig was less effective in preventing allograft fibrosis and was associated with a reduced Foxp3⁺ regulatory T cell population. These findings suggest that CTLA4-Ig plays a role in modulating T-cell responses and highlight the importance of early initiation of treatment in preventing CLAD.