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Abstract One hundred consecutive human renal allograft Tru-cut needle biopsies were studied for in vitro proliferation of T lymphocytes under restrictive culture conditions containing low does of recombinant interleukin. Each biopsy was entered into a blinded code and evaluated prospectively for visual evidence of growth at 24 hours and for sustained growth. Those T cell populations exhibiting sustained growth were then evaluated for cell surface phenotype by FACS; for allospecific cytotoxicity by release; for a proliferative response to alloantigen by incorporation and for secretion of IL2, IL4, interferon-y, and Tumor Necrosis Factor in Response tp alloantigenic stimulation by ELISA. All results were compared with clinical diagnosis, immunosuppression at the time of biopsy, diagnosis and phenotyping by immunophathology, short term outcome and long term graft survival. Growth at 24 hours was predictive of acute cellular rejection (p 0.0005), unrelated to chronic rejection (p=0.663) or maintenance immunosuppression (p=0.911), and inversely correlated with cyclosporine toxicity (p=0.051) and treatment with OKT3 (p=0.014). The CD4/CD8 ratio of the sustained T cell populations was unrelated to that seen on histological examination (correlation coefficient = 0.098 and 0.044 for diffuse and aggregate infiltrates, respectively). Cytotoxic specificity for HLA class II was mediated by CD4+ cells and for HLA class I by CD8+ cells. Enhanced secretion of IL2 in response to alloantigen distinguished those cells. |