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 (GIC) 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 anti-class 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.