BackgroundCellular rejection of an allograft is mediated in part by peripheral blood T cells. We tested the hypothesis that quantitative changes in T-cell subsets can be detected in the peripheral blood and that these changes correlate with rejection.Methods and ResultsT-cell subset analysis was performed by flow cytometry using monoclonal antibodies recognizing six isotypic epitopes of the T-cell receptor β-chain variable (V) region. These analyses were done at 7-day (mean) time intervals. Fluctuations within a given subset were determined by dividing the number of positive cells observed by the number of positive cells found on the previous analysis. For healthy volunteers observed over a period of 30 days, 119 of 120 subset ratios (99.2%) fell between 0.5 and 2.0. For patients, 57 of 240 subset ratios (23.8%) fell outside of this range (P<.004,X2). The occurrence of the abnormal ratios coincided more closely with cellular rejection (mean±SD, 7.7±6.2 days from a positive biopsy; median, 5 days; range, 0 to 28 days) than did the occurrence of normal subset ratios (mean±SD, 14.4±10.9 days from a positive biopsy; median, 11 days; range, 0 to 44 days;P<.005 by Mann-WhitneyUtest). Regression analysis confirmed a significant (P<.001,R=.91) temporal association between cellular rejection and abnormal subset fluctuations. No correlation was found between abnormal subset ratios and either vascular rejection or use of high-dose prednisone.ConclusionsT-cell subset measurement may be a method of noninvasive monitoring of cellular rejection after transplantation and may provide insights into the physiology of graft rejection with the potential for the development of more specific immunosuppressive therapy.