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CD4 T Cell-Mediated Rejection of Cardiac Allografts in B Cell-Deficient Mice¹

Taiji Nozaki^*,, Joshua M. Rosenblum^,, Daisuke Ishii^*,, Kazunari Tanabe and Robert L. Fairchild^2,*,,

^* Glickman Urological and Kidney Institute and Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195; Department of Urology, Tokyo Women’s Medical University, Tokyo, Japan; and Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106

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.µMT^–/– recipients depleted of CD8 T cells. Isolated wild-type C57BL/6 and B6.µMT^–/– CD4 T cells had nearly equivalent in vivo alloreactive proliferative responses. CD4 T cell numbers in B6.µMT^–/– 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.µMT^–/– 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.µMT^–/– CD4 T cells to reject cardiac allografts. These results indicate that the low number of splenic CD4 T cells in B6.µMT^–/– 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants (AI40459 and AI51620) from the National Institutes of Allergy and Infectious Diseases and Grant 60495086 from the Roche Organ Transplant Research Foundation.

² Address correspondence and reprint requests to Dr. Robert L. Fairchild, Lerner Research Institute, NB3-79, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195-0001. E-mail address: fairchr{at}ccf.org