CORRELATION BETWEEN CELLULAR REJECTION OF CARDIAC ALLOGRAFTS AND QUANTITATIVE CHANGES AMONG T-CELL SUBSETS IDENTIFIED BY V-BETA EPITOPE EXPRESSION

Background Cellular rejection of an allograft is mediated in part by p eripheral blood T cells. We tested the hypothesis that quantitative ch anges in T-cell subsets can be detected in the peripheral blood and th at these changes correlate with rejection. Methods and Results T-cell subset analysis was performed by flow cytometry using monoclonal antib odies recognizing six isotypic epitopes of the T-cell receptor beta-ch ain variable (V) region. These analyses were done at 7-day (mean) time intervals. Fluctuations within a given subset were determined by divi ding the number of positive cells observed by the number of positive c ells found on the previous analysis. For healthy volunteers observed o ver 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 outsi de of this range (P<.004, X(2)). 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 da ys from a positive biopsy; median, 11 days; range, 0 to 44 days; P<.00 5 by Mann-Whitney U test). Regression analysis confirmed a significant (P<.001, R=.91) temporal association between cellular rejection and a bnormal subset fluctuations. No correlation was found between abnormal subset ratios and either vascular rejection or use of high-dose predn isone. Conclusions T-cell subset measurement may be a method of noninv asive monitoring of cellular rejection after transplantation and may p rovide insights into the physiology of graft rejection with the potent ial for the development of more specific immunosuppressive therapy.