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Transplantation of the intestine means transplantation of viable donor lymphocytes into the recipient. Therefore, in addition to rejection, there is the possibility of graft-vs-host disease (GVHD).1 More potent immunosuppressants, such as FK 506, have made successful clinical small bowel transplantation a reality.2 With improved clinical outcomes3 it is valuable to assess the functional capabilities of the lamina propria associated lymphocytes (LPAL). Our group has studied the LPAL from serial intestinal graft biopsies taken from a recipient who primarily receives FK 506 immunosuppression.
The patient is a 27-year-old woman who, secondary to a hypercoagulable state, thrombosed her mesenteric circulation resulting in necrosis of her small intestine. Liver failure was secondary to chronic total parenteral nutrition therapy. She received a liver/small intestine allograft from an ABO compatible donor. The patient was crossmatch negative. The patient remained free of rejection until postoperative day (POD) 34. She was treated successfully and had a normal biopsy at POD 55. There were no episodes of GVHD.
LPAL were propagated from serial proximal and distal mucosal biopsies by culturing divided biopsies for 2 weeks in RPMI 1640 plus 5% human AB serum, and 30 U/mL recombinant interleukin-2 (IL-2). Propagated LPAL from five serial biopsies of graft jejunum and ileum were tested for primed proliferative activity when challenged with irradiated donor splenocytes in a 3-day assay. Proliferative activity was measured as uptake of tritiated thymidine. Additional LPAL were tested for cytotoxic activity against donor splenocyte targets labelled with 51Cr in a standard 4-hour cell-mediated lympholysis assay.
Primed proliferative alloreactive T lymphocytes were propagated from four of eight biopsies that were declared histologically “normal” (Table 1). However, none of the eight normal biopsies yielded a population of T cells that were capable of killing donor targets (> 10% cytotoxicity). T lymphocytes propagated from biopsies taken during this patient’s one episode of rejection (POD 34) yielded both primed proliferative and cytotoxic alloreaetive T lymphocytes (Table 1). Follow-up biopsy at POD 55 (after solumedrol therapy) yielded neither proliferative nor cytotoxic lymphocytes.
Propagation of T cells demonstrating primed proliferative responses to donor antigens occurred nonspecifically throughout this patient’s postoperative course. These cells likely represent a very small and adequately suppressed population of immunocompetent lymphocytes infiltrating the graft lamina propria. Their potential capabilities are suppressed by local endogenous factors and/or therapeutic FK 506 concentrations. These cells lacked cytolytic capabilities when the patient was free of rejection; however when the patient rejected, donor-specific cytotoxic T cells were propagated. With improved clinical outcomes in human small intestine transplantation, more data can be accumulated to reveal the importance of the propagation of cytotoxic T cells from graft mucosal biopsies.
Supported by Project grant no. DK29961 from the National Institutes of Health, Bethesda, Maryland and the Pathology Education Research Fund (PERF).