Titration of donor CD4+ T-cell dose and induction of GVHD.
(A) CD4+ T cells from B6-cdd donors exhibit significant but delayed weight loss after BMT. BALB/c recipients were transplanted with 5 × 106 B6-Ly5.1 TCD–bone marrow cells by means of 2.5 × 106 and 0.25 × 106 CD4+ T cells from either wild-type B6 or B6-cdd donors (5 mice per group). The kinetic onset of weight loss showed that higher numbers of B6-cdd than of B6 CD4+ T cells were needed to induce a similar pattern. (B) CD4+ T cells from B6-cdd donors were less efficient in inducing lethality of recipients. Recipients of BMT described in Figure3A were monitored for survival rate. B6-cdd CD4+ T cells induced a delayed and lower mortality when recipients of the same numbers of wild-type B6 CD4+ T cells were compared. It was found that 5 × 106 B6-cdd CD4+ T cells induced 100% lethality (data not shown, n = 5). The lethality curves of 2.5 × 106 B6-cdd (■) versus 0.25 × 106 B6 (▾) were not significantly different (P = .1369). ■, 2.5 × 106 B6-cdd; ▿, 0.25 × 106 B6-cdd; ■, 2.5 × 106 B6; and ▾, 0.25 × 106 B6 donor CD4+ T cells.
