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1–3Gal1
Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
The majority of xenoreactive natural Abs in humans recognize the
carbohydrate Ag present on pig tissue, Gal
1–3Gal
1–4GlcNAc-R
(Gal), synthesized by the enzyme UDP
galactose:-D-galactosyl-1,4-N-acetyl-D-glucosaminide
(1–3)galactosyltransferase or GT. Using GT knockout mice
(GT0 mice), which like humans produce serum Abs that bind
Gal, we examined the role of T cells in production of Abs specific
for Gal. GT0 mice were crossed with TCR- knockout
mice (TCR-0) to generate double-knockout mice
(GT0/TCR-0). While
GT0/TCR-+ mice exhibited an age-dependent
increase in the serum titer of natural Abs specific for Gal, a
similar increase was not observed in
GT0/TCR-0 mice, and the titer of
Gal-specific Abs in double knockouts was significantly lower than in
age-matched GT0/TCR-+ mice. Immunization
with pig cells resulted in a significant increase in the serum titer of
Gal-specific Abs in GT0/TCR-+ mice, but
had no effect on the level of Gal-specific serum Abs in
GT0/TCR-0 mice. Treatment of
GT0/TCR-+ mice with anti-CD40L Abs
before immunization with pig cells prevented sensitization to Gal.
Our data suggest that the majority of Gal-specific Abs are T cell
dependent and that production of Gal-specific Abs after
sensitization can be prevented by blocking costimulatory
pathways.
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