HIGH-FREQUENCY OF IL-10-SECRETING CD4(+) GRAFT-INFILTRATING T-LYMPHOCYTES IN PROMPTLY REJECTED KIDNEY ALLOGRAFTS

IFN-gamma and IL-10 secretion by sorted T cell subsets of irreversibly rejected kidney graft-infiltrating cells (GIG) and normal PBMC was studied by ELISPOT. The low spontaneous frequency of IFN-gamma-producing cells (IFN-gamma-PC) was strongly increased by anti-CD3 activation within unsorted, CD3(+)CD4(+), and CD3(+)CD4(-) subsets of GIC and PBMC. In contrast with PBMC, IL-10-PC from GIC were at higher frequency within CD4(+) cells than among CD4(-) ones (P<0.03). Four kidneys removed after 3.7+/-0.8 months showed acute vascular rejection, high frequency of activated CD4(+) IL-10-PC (118+/-68 per 10(4) cells), and high percentage of anticlass II antibody reactivity (87.6+/-6.3%). In contrast, four patients with kidneys removed later (53.7+/-1.6 months, P=0.02) displayed chronic rejection with superimposed acute cellular rejection, low frequency of CD4(+) IL-10-PC (7.0+/-3.0 per 10(4) cells, P=0.02), and low percentage of anti-class II: antibody reactivity (12.9+/-6.1%, P=0.02). Thus, accelerated vascular rejection appears to be associated with preferential production of IL-10 by activated CD4(+) GIC, which may act by shifting the effector arms of alloreaction toward humoral responses.