H-2D HAPLOTYPE-LINKED EXPRESSION AND INVOLVEMENT OF TNF-ALPHA IN TH2 CELL-MEDIATED TISSUE INFLAMMATION

We recently reported that polyclonal anti-CD3 epsilon-pulsed Th2 cells mediate local tissue inflammation (DTH2) when injected into naive syn genic recipient mice, and that this response is entirely dependent on IL-4 in BALB/c (H-2(d)) mice. We now describe a different cytokine dep endence in mice that bear a H-2(b) MHC haplotype. Injection of either soluble IL-4R (sIL-4R) or anti-TNF Ab partially inhibited swelling tha t was mediated by Th2 cells from high TNF-producing C57BL/6 mice. Anti -TNF and sIL-4R in combination were required to completely abrogate th e swelling reaction and cellular infiltrate. Adoptive transfers across strain barriers showed that the TNF dependence was dictated by the or igin of the transferred cells, rather than by the recipient. Experimen ts with intra-H-2 recombinant C57BL/10 strains indicated that TNF rele ased by Th2 cells was correlated with the involvement of TNF in DTH2:T h2 cells from the H-2D(b) strains C57BL/10 and B10.A(2R) produced high amounts of bioactive TNF and mediated swelling that was partially inh ibited by anti-TNF. In contrast, Th2 cells from B10.D2 and B10.A mice (H-2D(d)) produced low levels of TNF, and anti-TNF had no effect on DT H2 in these strains. Our results suggest a linkage between the TNF dep endence of DTH2, the capacity of Th2 cells to release TNF upon restimu lation, and the donor H-2D haplotype; strain-dependent allelic express ion of TNF seems to determine the involvement of this cytokine in DTH2 .