Compatibility of porcine and human interleukin 2: implications for xenotransplantation.
BACKGROUND
Xenotransplantation provides a possible solution to the severe shortage of allogeneic organ donors. The pig, which shares many physiological similarities with humans, makes it an optimal species for preclinical experimentation and clinical applications. Interleukin 2 (IL2) is a potent growth factor secreted primarily by T helper lymphocytes and it is vital to the cellular expansion required for a productive immune response and the development and peripheral expansion of CD4+CD25+ regulatory T cells. Therefore, it is essential to understand of the compatibility of IL2 between pigs and humans.


METHODS
We first compared the cDNA and protein sequences and the crystal structures of human and porcine IL2 and IL2 receptors, respectively. The effect of IL2 to induce T cell proliferation was determined by 3H-thymidine incorporation and cell cycle detection.


RESULTS
Porcine IL2 induced very limited proliferation of human lymphocytes while it functioned well on porcine lymphocytes. Human IL2 had remarkably reduced effects on porcine lymphocytes whereas it worked well on human lymphocytes.


CONCLUSIONS
Our present study showed that the interaction of IL2 and IL2R across species might have defects. Together with the wide physiological functions of IL2, our data indicated that physiological disorders could be caused by the poor function of xenogeneic donor IL2 on host cells in full hematopoietic chimera. Our data suggested an additional potential advantage for the mixed xenogeneic chimeras.
Zhang
Baojun
B
State Key Laboratory of Biomembrane and Membrane Biotechnology, Transplantation Biology Research Division, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Ge
Basheng
B
Xia
Xuepei
X
Liu
Jun
J
Sun
Liguang
L
Rao
Enyu
E
Zhao
Yong
Y
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D007376:Interleukin-2