Unaltered graft survival and intragraft lymphocytes infiltration in the cardiac allograft of Cxcr3-/- mouse recipients.
Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3(-/-) mice. Interestingly, in our hands, neither of the independently derived Cxcr3(-/-) lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-gamma production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3(-/-) recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.
Kwun
J
J
Division of Transplantation, Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA.
Hazinedaroglu
S M
SM
Schadde
E
E
Kayaoglu
H A
HA
Fechner
J
J
Hu
H Z
HZ
Roenneburg
D
D
Torrealba
J
J
Shiao
L
L
Hong
X
X
Peng
R
R
Szewczyk
J W
JW
Sullivan
K A
KA
DeMartino
J
J
Knechtle
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054367:Receptors, CXCR3 / Q000378:metabolism*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D007371:Interferon-gamma