Involvement of T lymphocyte subsets in the rejection of murine tumors by syngeneic or autologous hosts
Sammanfattning: Involvement of T Iymphocyte subsets in the rejection of murinetumors by syngeneic or autologous hosts Tao Wen The aim of this thesis is to study the requirement of CD4+ and CD8+ T Iymphocytesubset, CD28 costimulatory molecule and p56kk for the rejection of syngeneic tumorgrafts, and the autochthonous tumors induced by Moloney murine sarcoma virus. Italso addresses the role of CD4+ and CD8+ T subsets with regard to the polyomaviruspersistence and tumor development. CD4-, CD8-, CD8-/4-, CD28- and p56kk-knockoutmice were used as syngeneic or autologous animal models. In tumor transplantion rejection experiment, deficiency of either CD8+ or CD4+T cells abrogated the protective immunity against ALC Iymphoma grafts, but not againstMC57X fibrosarcoma. MC57X-specific TNF-a release was induced in preimmunized syngeneicCD8-/- or CD4-/- mice. MMSV induced primary sarcoma regressed in all CD4-/- mice, but about half of CD8-/-mice developed progressive tumors. MMSV tumor regression was abolished in CD8-/-4-/-double knockout mice. Deficiency of B cells and antibody production did not affectMMSV tumor regression. When adult mice were infected with polyomavirus, deficiency of either CD4+ orCD8+ T subset did not affect the clearance of the virus, but the viral persistencewas established in CD4-/-8-/- double knockout mice. When newborn mice were infected,polyoma tumor incidence was significantly increased in CD4-/-8-/- double knockoutmice. ALC and MC57X tumors were rejected by preimmunized syngeneic CD28-/ mice. MMSV-inducedprimary sarcoma regressed in CD28-/- hosts. However, the spontanous regression ofB7-transfected EL-4 Iymphoma was abrogated by CD28 deficiency. Tumor- or virus-specificCTLs, as well as TNF release, were able to be induced in the CD28 knockout mice. In p56kk-deficient mice, protective immunity against MC57X was abolished, andMHC-incompatible or minor-different skin grafts were tolerated. Natural killer remainsnormal. Taken togather, the requirement of CD4+, CD8+ T subsets and CD28 costimulationis differential, depending on the type of tumor and the anti-tumor immune response. Key word: CD8, CD4, CD28, p56kk, tumor rejection, MMSV, polyomavirus, B7, knockoutmice ISBN-91 -628-2836-3
Denna avhandling är EVENTUELLT nedladdningsbar som PDF. Kolla denna länk för att se om den går att ladda ner.