Blocking the CD28-B7 T cell costimulation pathway induces long term cardiac allograft acceptance in the absence of IL-4.
Blocking the CD28-B7 T lymphocyte costimulatory pathway with the recombinant protein CTLA4Ig induces long term allograft survival in rodents. It has been suggested that this results from selective activation of the Th2 immune pathway. To test this hypothesis, we compared vascularized cardiac allograft survival in wild-type (IL-4 +/+) and homozygous IL-4 gene-knockout (IL-4 -/-) mice. We report in this study that long term survival (>100 days) of fully allogeneic grafts can be induced readily in IL-4 -/- recipients treated with a short course of CTLA4Ig. We also demonstrate that IL-4 -/- mice are deficient in Th2-type cytokine expression following in vitro or in vivo allostimulation. These results suggest that IL-4 production and subsequent generation of a Th2-type immune response are not obligatory for CTLA4Ig-induced long term acceptance of vascularized allografts.
Lakkis
F G
FG
Department of Medicine (Renal Division), Emory University School of Medicine, Atlanta, GA 30033, USA.
Konieczny
B T
BT
Saleem
S
S
Baddoura
F K
FK
Linsley
P S
PS
Alexander
D Z
DZ
Lowry
R P
RP
Pearson
T C
TC
Larsen
C P
CP
D000069594:Abatacept; D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000627:therapeutic use; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D006082:Graft Enhancement, Immunologic; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D007519:Isoantigens / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013154:Spleen / Q000473:pathology; D018418:Th2 Cells / Q000473:pathology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007166:Immunosuppressive Agents; D007519:Isoantigens; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D000069594:Abatacept