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Antiviral Cytotoxic Activity Across a Species Barrier in Mixed Xenogeneic Chimeras: Functional Restriction to Host MHC¹

Yolonda L. Colson^*, Ralph A. Tripp, Peter C. Doherty, Sherry M. Wren^§, Michael Neipp^§, Ashraf Y. Abou El-Ezz^§ and Suzanne T. Ildstad^2,§

^* Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261; Centers of Disease Control and Prevention, Atlanta, GA 30033; Department of Immunology, St. Jude’s Research Hospital, Memphis, TN 38101; and ^§ Institute for Cellular Therapeutics, Allegheny University of Health Sciences, Philadelphia, PA 19102

Reconstitution of lethally irradiated mice with a mixture of mouse and rat bone marrow cells (mouse + ratmouse) results in mixed xenogeneic chimerism and donor-specific tolerance. The current study demonstrates that mouse and rat T lymphocytes that have developed in xenogeneic chimeras are restricted to Ag presentation by mouse, but not rat, APC. Restriction to host Ags results in functional immunocompetence with generation of antiviral cytotoxic activity in vivo, within and across species barriers. These data demonstrate for the first time that the host thymus is sufficient to support development and positive selection of functional cross-species T lymphocytes. The superior immunocompetence, as compared with fully xenogeneic (ratmouse) chimeras, may prove to be of significant benefit in the clinical application of xenotransplantation to solid organ transplantation and immune reconstitution for AIDS.

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