Disparate primary and secondary allospecific CD8+ T cell cytolytic effector function in the presence or absence of host CD4+ T cells.
The role of CD4+ T cells in promoting CD8+ T cell effector activity in response to transplant Ags in vivo has not been reported. We used a hepatocellular allograft model known to initiate both CD4-dependent and CD4-independent rejection responses to investigate the contribution of CD4+ T cells to the development, function, and persistence of allospecific CD8+ T cell effectors in vivo. Complete MHC-mismatched hepatocellular allografts were transplanted into C57BL/6 (CD4-sufficient) or CD4 knockout (CD4-deficient) hosts. The development of in vivo allospecific cytotoxicity was determined by clearance of CFSE-labeled target cells. CD8+ T cell cytotoxic effector activity was enhanced in response to allogeneic hepatocellular grafts with a greater magnitude of allocytotoxicity and a prolonged persistence of CTL effector activity in CD4-sufficient hosts compared with CD4-deficient hosts. Cytolytic activity was mediated by CD8+ T cells in both recipient groups. In response to a second hepatocyte transplant, rejection kinetics were enhanced in both CD4-sufficient and CD4-deficient hepatocyte recipients. However, only CD4-sufficient hosts developed recall CTL responses with an augmented magnitude and persistence of allocytotoxicity in comparison with primary CTL responses. These studies show important functional differences between alloreactive CD8+ T cell cytolytic effectors that mature in vivo in the presence or absence of CD4+ T cells.
Horne
Phillip H
PH
Department of Surgery, Comprehensive Transplant Center, Ohio State University Medical Center, 1654 Upham Drive, Columbus, OH 43210, USA.
Koester
Mitchel A
MA
Jayashankar
Kartika
K
Lunsford
Keri E
KE
Dziema
Heather L
HL
Bumgardner
Ginny L
GL
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D007519:Isoantigens / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015704:CD4 Antigens; D007519:Isoantigens