title: Positive and negative selection of functional mouse CD4 cells by porcine MHC in pig thymus grafts.
abstract: Specific tolerance to discordant xenogeneic donors can be achieved by grafting of fetal pig thymic and liver tissue (FP THY/LIV) to T cell and NK cell-depleted, thymectomized (ATX) mice. Mouse CD4+ T cells develop in FP THY/LIV grafts, and demonstrate remarkably normal immune function, including host-restricted responses to keyhole limpet hemocyanin. We have therefore studied the role of host MHC class II in the development of mouse T cells in FP THY/LIV grafts by comparing their development in ATX MHC class II-deficient (IIKO) and wild-type (H-2b) mice. Mouse CD4+ T cells repopulated T/NK cell-depleted, ATX IIKO mice after grafting with FP THY/LIV, indicating that pig MHC can positively select mouse CD4 cells. Expression of TCR, MHC class I, Qa-2, heat-stable Ag, and CD45RB among double-positive and CD4 single-positive (SP) graft thymocytes in wild-type recipients was similar to that in normal mouse thymi, whereas CD4 SP thymocytes in grafts of IIKO mice showed increased Qa-2 and decreased heat-stable Ag expression, suggesting an increased level of maturity. Double-positive cells in grafts of IIKO mice also expressed higher than normal levels of Qa-2. Deletion within the grafts of Vbeta3+, Vbeta5.1/5.2+, and Vbeta11+ but not Vbeta6+, Vbeta7+, or Vbeta8.1/8.2+ mouse CD4 SP thymocytes in ATX IIKO mice demonstrated that swine leukocyte Ag participates in negative selection of the T cell repertoire. Therefore, porcine MHC mediates positive and negative selection of mouse thymocytes, but host class II MHC molecules also regulate thymocyte maturation in xenogeneic thymic grafts.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: J J
authors.initials: JJ
authors.lastname: Sergio
authors.forename: K
authors.initials: K
authors.lastname: Swenson
authors.forename: J S
authors.initials: JS
authors.lastname: Arn
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: M
authors.initials: M
authors.lastname: Sykes
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D017637:Clonal Deletion; D005802:Genes, MHC Class II; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D007108:Immune Tolerance / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013552:Swine; D013556:Swine, Miniature; D013934:Thymectomy; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta