B. Olack et al., Indirect recognition of porcine swine leukocyte Ag class I molecules expressed on islets by human CD4(+) T lymphocytes, J IMMUNOL, 165(3), 2000, pp. 1294-1299
Xenotransplantation of porcine islets is considered a viable alternative tr
eatment for type 1 diabetes mellitus, Therefore, we characterized human PBL
responding to porcine islets both in vitro by coculture and in vivo using
SCID mice reconstituted with human PBLs (HuPBL-SCID) and transplanted with
porcine islets. T cell lines generated in vitro and graft-infiltrating T ce
lls obtained from HuPBL-SCID mice were CD4(+)-proliferated specifically to
porcine islets cultured with autologous APC. This proliferation was abrogat
ed by an anti-human class II Ab, These T cell lines also proliferated to pu
rified swine leukocyte Ag (SLA) class I molecules in the presence of self-A
PC, indicating that the primary xenoantigens recognized are peptides derive
d from SLA, This CD4(+) T cell line lysed porcine islets but not splenocyte
s. CD4(+) T cell clones with Th0, Th1, and Th2 cytokine profiles were isola
ted. The Th0 and Th1 clones lysed porcine islets, whereas the Th2 clone tha
t secreted a large amount of IL-4 was not lytic, These results demonstrate
that human T cells responding to porcine islets are primarily CD4(+) and re
cognize porcine xenoantigens by the indirect Ag pathway presentation. These
activated T cells produce cytokines that lyse islets, Furthermore, we demo
nstrate that the major porcine xenoantigens recognized are SLA class I mole
cules.