Details

Autor(en) / Beteiligte

• Dodd‐o, J. M.
• Lendermon, E. A.
• Miller, H. L.
• Zhong, Q.
• John, E. R.
• Jungraithmayr, W. M.
• D’Alessio, F. R.
• McDyer, J. F.

Titel

CD154 Blockade Abrogates Allospecific Responses and Enhances CD4+ Regulatory T‐Cells in Mouse Orthotopic Lung Transplant

Ist Teil von

• American journal of transplantation, 2011-09, Vol.11 (9), p.1815-1824

Ort / Verlag

Malden, USA: Blackwell Publishing Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Acute cellular rejection (ACR) is a common and important clinical complication following lung transplantation. While there is a clinical need for the development of novel therapies to prevent ACR, the regulation of allospecific effector T‐cells in this process remains incompletely understood. Using the MHC‐mismatched mouse orthotopic lung transplant model, we investigated the short‐term role of anti‐CD154 mAb therapy alone on allograft pathology and alloimmune T‐cell effector responses. Untreated C57BL/6 recipients of BALB/c left lung allografts had high‐grade rejection and diminished CD4+: CD8+ graft ratios, marked by predominantly CD8+>CD4+ IFN‐γ+ allospecific effector responses at day 10, compared to isograft controls. Anti‐CD154 mAb therapy strikingly abrogated both CD8+ and CD4+ alloeffector responses and significantly increased lung allograft CD4+: CD8+ ratios. Examination of graft CD4+ T‐cells revealed significantly increased frequencies of CD4+CD25+Foxp3+ regulatory T‐cells in the lung allografts of anti‐CD154‐treated mice and was associated with significant attenuation of ACR compared to untreated controls. Together, these data show that CD154/CD40 costimulation blockade alone is sufficient to abrogate allospecific effector T‐cell responses and significantly shifts the lung allograft toward an environment predominated by CD4+ T regulatory cells in association with an attenuation of ACR. The authors find that CD154/CD40 costimulation blockade alone in a mouse model of orthotopic lung transplant results in abrogation of allospecific T‐cell responses and increased regulatory T cells.