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CXCL9 Antagonism Further Extends Prolonged Cardiac Allograft Survival in CCL19/CCL21‐Deficient Mice
Author(s) -
Colvin Bridget L.,
Wang Zhiliang,
Nakano Hideki,
Wu WenHan,
Kakiuchi Terutaka,
Fairchild Robert L.,
Thomson Angus W.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00996.x
Subject(s) - ccl19 , medicine , dendritic cell , chemokine , t cell , lymph node , immunology , heart transplantation , lymphatic system , transplantation , pathology , immune system , chemokine receptor
CCL19/MIP‐3β and CCL21/SLC are essential for chemotactic recruitment of mature dendritic cells (DC) to T‐cell areas of secondary lymphoid tissue. P aucity of l ymph node T‐cell s ( plt/plt ) mice lack CCL21‐serine (ser) and CCL19 expression. We tested plt/plt and wild type (wt) BALB/c (H2 d ) mice as recipients of heart or skin allografts from C57BL/10J (H2 b ) donors. Donor DC trafficking to secondary lymphoid tissue was markedly reduced in plt heart but not skin allograft recipients. Heart, but not skin grafts survived significantly longer in plt recipients. Accordingly, T cells from plt heart transplant recipients demonstrated poor anti‐donor responses in ex vivo MLR, compared to wt heart or wt and plt skin recipients. Moreover, donor‐reactive T cells from plt heart recipients exhibited Th2‐skewing in comparison to T cells from wt heart or skin graft recipients. Anti‐CXCL9/Mig was administered for 2 weeks post‐transplant to determine whether impairment of activated T‐cell migration could further prolong cardiac allograft survival in plt recipients. CXCL9‐antagonism extended graft survival significantly only in plt mice, likely due, in part, to retention of alloactivated T cells in secondary lymphoid tissue/reduction of graft‐infiltrating T cells. Thus, targeting DC and activated T‐cell migration concomitantly has additive effects in prolonging heart graft survival with potential for therapeutic application.