Growth of SJL/J-derived transplantable reticulum cell sarcoma as related to its ability to induce T-cell proliferation in the host. I. Dominant negative genetic influences of other parent haplotype in F1 hybrids of SJL/J mice.

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Abstract
Growth of 3 transplantable reticulum cell sarcomas (RCS) was studied in a variety of F1 hybrids of SJL/J mice by determination of lymph node (LN) and spleen:body weight ratios 7 and 14 days after i.v. injection of RCS cells. Comparison of BI.ovrhdot.O.S .times. SJL and A.SW .times. SJL with SJL/J showed a negative effect of A and the BIO non-H-2 genes, particularly on growth in LN. F1 hybrid resistance was noted with F1 hybrids that carried H-2Dd and was much more evident with F1 hybrids from BIO- than from A-background mice. This resistance was less marked at 14 than at 7 days and was partially overcome by injection of higher tumor doses. Changing the I region in the F1 parent from H-2s to H-2b or H-2f had no effect on growth, but changing to H-2k or H-2d virtually abolished the ability to support tumor growth. This effect appeared to be partially a result of the I-E/C and partially of the I-A(B) region and was not overcome by higher tumor dose or longer intervals after injection. There also appeared to be a negative influence on H-2Kk growth, but this was difficult to differentiate from the I-Ak effect with the available strains. The known proliferative responsiveness that SJL/J Lyt-1 T [thymus-derived] cells exhibit to Ia [immune response-associated] determinants on .gamma.-irradiated RCS cells in vitro was also compared with that of cells from various F1 hybrids. Responsiveness of F1 LN cells was expressed as a percentage of the response in SJL/J LN cells to the same RCS cells, measured as [3H]thymidine incorporation. There was a striking degree of correlation between proliferative responsiveness of F1 LN cells to RCS and the ability of the F1 mice to support tumor growth. This correlation was especially clear with respect to the negative influences of non-H-2 genes and of H-2 loci in the I region, particularly of I-Ak or -d and of I-E/Ck or -d, but there also appeared to be a (smaller) negative effect of I-Ab or -f. Negative influence of H-2Dd on growth was not reflected in a similarly large effect on the proliferative response. Additional findings showed that LN cells from all F1 hybrids exhibited equivalent syngeneic mixed lymphocyte responses in the presence of polyethylene glycol to mitomycin-treated spleen cells from both the SJL/J and the other parent. The extra high response of F1 cells to RCS cells as compared with SJL spleen cells was always absent when Ik or -d was contributed by one of the F1 parents. A promoting effect of the proliferative response on RCS growth in vivo was suggested, as was an interesting effect of I-A and I-E/C genes, possibly via an interaction product, on the ability of LN cells to be stimulated by Ia determinants on RCS cells.