CD4 T cell-mediated rejection of cardiac allografts in B cell-deficient mice.
CD4 T cell-dependent mechanisms promoting allograft rejection include expression of inflammatory functions within the graft and the provision of help for donor-reactive CD8 T cell and Ab responses. These studies tested CD4 T cell-mediated rejection of MHC-mismatched cardiac allografts in the absence of both CD8 T and B lymphocytes. Whereas wild-type C57BL/6 recipients depleted of CD8 T cells rejected A/J cardiac grafts within 10 days, allografts were not rejected in B cell-deficient B6.muMT(-/-) recipients depleted of CD8 T cells. Isolated wild-type C57BL/6 and B6.muMT(-/-) CD4 T cells had nearly equivalent in vivo alloreactive proliferative responses. CD4 T cell numbers in B6.muMT(-/-) spleens were 10% of that in wild-type mice but were only slightly decreased in peripheral lymph nodes. CD8 T cell depletion did not abrogate B6.muMT(-/-) mice rejection of A/J skin allografts and this rejection rendered these recipients able to reject A/J cardiac allografts. Redirection of the alloimmune response to the lymph nodes by splenectomy conferred the ability of B6.muMT(-/-) CD4 T cells to reject cardiac allografts. These results indicate that the low number of splenic CD4 T cells in B6.muMT(-/-) mice underlies the inability to reject cardiac allografts and this inability is overcome by diverting the CD4 T cell response to the peripheral lymph nodes.
Nozaki
Taiji
T
Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Rosenblum
Joshua M
JM
Ishii
Daisuke
D
Tanabe
Kazunari
K
Fairchild
Robert L
RL
D000818:Animals; D001402:B-Lymphocytes; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D049109:Cell Proliferation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D014181:Transplantation Immunology; D014184:Transplantation, Homologous