title: Selective resistance of CD44hi T cells to p53-dependent cell death results in persistence of immunologic memory after total body irradiation.
abstract: Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation markedly changes the balance of residual T cell subsets to favor CD4(+)CD44(hi) NKT cells because of the differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results showed that CD4(+) T cells were markedly more resistant than CD8(+) T cells, and CD44(hi) T cells, including NKT cells and memory T cells, were markedly more resistant than CD44(lo) (naive) T cells. The memory T cells immunized to alloantigens persisted even after myeloablative (1000 cGy) TBI and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1000 cGy was prevented in p53(-/-) mice, there was progressive T cell death in p53(-/-) mice at higher doses. Although p53-dependent T cell death changed the balance of subsets, p53-independent T cell death did not. In conclusion, resistance of CD44(hi) T cells to p53-dependent cell death results in the persistence of immunological memory after TBI and can explain the immune-mediated rejection of marrow transplants in sensitized recipients.
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jones
authors.forename: Holbrook
authors.initials: H
authors.lastname: Kohrt
authors.forename: Samuel
authors.initials: S
authors.lastname: Strober
mesh_terms: D000818:Animals; D016923:Cell Death / Q000276:immunology / Q000528:radiation effects; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018960:Hyaluronan Receptors / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism; D014916:Whole-Body Irradiation
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D016159:Tumor Suppressor Protein p53