Activation or suppression of bactericidal activity of macrophages during a graft-versus-host reaction against I-A and I-J-region differences, respectively.

Systemic graft-versus-host reactions (GVHR) were induced in F1 heterozygous mice by injecting 10(8) parental lymphocytes. The Anti-Thy 1.2-sensitive, T-cell mediated activation of macrophages was assessed by their increased capacity to destroy a facultative intracellular bacterium Listeria monocytogenes. The difference in MHC regions causing a GVHR that induced high levels of macrophage activation mapped to I-A. In contrast, differences at K or D, in any of the other H-2 subregions or in the non-H-2 background, including Mls alone or in combination, did not induce a GVHR leading to macrophage activation, unless these differences were combined with a difference at I-A. The numbers of parental cells needed to activate macrophages via a GVHR caused by I-A vs. non-I-A differences, varied at least 30- to 100-fold. When parental cells were injected into F1 offspring of parents differing at I-J, growth of Listeria was enhanced significantly; this negative effect on macrophages was not seen when parental combinations differing at I-A alone were compared with those differing at I-A plus I-J or I-J plus other H-2 regions.