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CD45 Congenic Bone Marrow Transplantation: Evidence for T Cell–Mediated Immunity

^a Institute for Cellular Therapeutics, University of Louisville, Louisville, Kentucky, USA;
^b Department of General and Thoracic Surgery, University of Kiel, Kiel, Germany

Key Words. Hematopoietic microenvironment • Niche • Nonmyeloablative conditioning • CD45 • Congenic bone marrow transplantation • Chimerism

Correspondence: Suzanne T. Ildstad, M.D., University of Louisville, 570 South Preston Street, Suite 404, Louisville, Kentucky 40202-1760, USA. Telephone: 502-852-2080; Fax: 502-852-2079; e-mail: stilds01{at}louisville.edu

CD45 congenic mice have been used to study stem cell engraftment in the absence of alloreactivity. Recently, impaired engraftment was reported in this model and attributed to weak immune reactivity. We have confirmed that there is indeed low-level reactivity mediated by CD8⁺ cells and ß-TCR⁺ T cells. B6 (CD45.2) recipients were conditioned with total body irradiation (TBI) and transplanted with increasing doses of B6 (CD45.1) bone marrow cells (BMCs). Although chimerism was present at 1 month in all recipients, durable engraftment did not occur with <150 cGy of TBI, emphasizing the importance of long-term follow-up in evaluating nonmyeloablative conditioning approaches. A single dose of cyclophosphamide on day 2 also significantly enhanced engraftment. When B6 TCRß^–/–, TCR^–/–, or TCRß^–/–/^–/– (CD45.2) mice were transplanted with CD45.1 bone marrow, significantly enhanced engraftment occurred in recipients lacking ß-TCR⁺ T cells (p < .00005). Similarly, removal of ß-TCR⁺ host T cells in wild-type recipients resulted in enhanced engraftment. Engraftment was also significantly increased in CD8^–/– and CD4^–/–/8^–/– recipients (p < .0005). Taken together, these results demonstrate that ß-TCR⁺ and CD8⁺ T cells play a critical role in regulating engraftment of CD45 congenic marrow and suggest that these cells are the main effector cells in low-level alloreactivity to the CD45 disparity.

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