[CITATION][C] Induction of Immunity and of Unresponsiveness to Parental Marrow Grafts in Adult F1 Hybrid Mice

G Cudkowicz, JH Stimpfling - Nature, 1964 - nature.com
G Cudkowicz, JH Stimpfling
Nature, 1964nature.com
* Mean uptake values are given as percentage of the total*** IUdR radioactivity adrtinistered
it: SE of the means, in excess of percentage retention of radioactivity in spleens of irradiated
control animals not injected with marrow. The number of recipient mice is indicated in
brackets; data of se veralindependent experiments were pooled. parentage (Fig. 1, curve A,
and Table 1). Thus, the simple substitution of the H–2% allele with H–23 conferred to the
marrow cells of B 10-D2 mice the ability to grow optimally in H-2 heterozygotes, although the …
* Mean uptake values are given as percentage of the total*** IUdR radioactivity adrtinistered it: SE of the means, in excess of percentage retention of radioactivity in spleens of irradiated control animals not injected with marrow. The number of recipient mice is indicated in brackets; data of se veralindependent experiments were pooled. parentage (Fig. 1, curve A, and Table 1). Thus, the simple substitution of the H–2% allele with H–23 conferred to the marrow cells of B 10-D2 mice the ability to grow optimally in H-2 heterozygotes, although the genetic background remained essentially that of the BI O strain. Conversely, substitution of the H–2* allele with H–23 conferred on the marrow cells of C3H-SW mice the trait for deficient growth in H–2 heterozygotes, despite the C3H genetic background of such mice. Differences in strength of hybrid resistance were noticeable, however, on comparison of the uptake-cell dose responses in F, hybrids from B 10 or C3H parents (Fig. 1, lines B and C). This observation raises the question whether or not the strength of hybrid resistance is modified by the genetic background of the parental strains entering the F", cross. Alternatively, the observed differences in strength of hybrid resistance might reflect dissimilarities in the K region of H–23 and H–2* with regard to the factor (s) involved in hybrid resistance.
Since H–2 isoantigens are thought to be of primary importance in deciding the fate of allogeneic tissue grafts*", it is conceivable that the H–2 controlled hybrid resistance may reflect differences in isoantigenic constitution between the tissues of H–24/H–2% parental mice and those of their heterozygous hybrid recipients. If this were the case, one would expect that hæmopoietic cells of the strains B10 and C3HS W would be antigenic to their resistant hybrids and capable of inducing a state of sensitivity or of unresponsiveness in such hybrids towards parental marrow grafts. To test this possibility, adult hybrid mice were given one of the following treatments before irradiation and infusion with parental marrow cells:(l) intraperitoneal injection at weekly intervals of 1-5 x 10" nucleated, viable parental marrow cells for a total of three injections;(2) intraperitoneal injection at weekly intervals of 2 x 10 nucleated, viable parental spleen cells for a total of four injections;(3) transplantation on to the mid-dorsal region of parental skin tissue taken from the donor's ear; and (4) intra-peritoneal injection at weekly intervals of Tyrode's solution for a total of three or four injections. Seven days after the last of the cellinjections, or 100 days after placing tho parental skin grafts (accepted and in perfect condition throughout), the hybrids were irradiated and infused with a single fixed dose of parental strain or allogeneic strain marrow cells. Five days later the extent of grafted marrow proliferation was assessed by the*** IUdR assay. To detect immunity, that is, an induced state in which parental marrow grafts become unacceptable to F". recipients which otherwise would accept them, we grafted a dose of parental marrow cells known to override the
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