Abu-Elmagd, K

Block, G

Demetris, AJ

Duquesnoy, R

Reyes, J

Starzl, TE

Suwan, S

Todo, S

Tzakis, A

Uknis, ME

Van Thiel, D

Zeevi, A

English

PubMed

D-Scholarship@Pitt

/3'/0 Analysis of Graft Lamina Propria Associated Lymphocytes ':;;;.",1,... a Recipient of a Human Cadaveric Small Bowel Allograft marily Immunosuppressed With FK 506 .E. Uknis, K. Abu-Elmagd, S. Suwan, G. Block, D. Van Thiel, J. Reyes, A. Tzakis, A.J. Demetris, S. Todo, Starzl, R. Duquesnoy, and A. Zeevi SPLANT A TION of the intestine means trans--_plantation of viable donor lymphocytes into the re-Therefore, in addition to rejection, there is the ----, ... "". of graft-vs-host disease (GVHD). I More potent JmmUnO!lUp,pn:ssl:mt:s. such as FK 506, have made success-clinical small bowel transplantation a reality. 2 With ;imlnm'ved 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. patient is a 27-year-old woman Who, secondary to a ,hypercoagulable state, thrombosed her mesenteric circu-'lation 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. MATERIALS AND METHODS LP AL were propagated from serial proximal and distal mucosal biopsies by culturing divided biopsies for 2 weeks in RPMI 1640 plus 5% human AD serum, and 30 U/mL recombinant interleu-kin-2 (lL-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 From the Departments of Pathology (M.E.U., 5.5 .• A.J.D .• R.D., A.Z.), Surgery (K.A.-E., D.V.T., J.R., A.T .• S.T., T.E.S.), and Medicine (G.B.). University Health Center of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania. Supported by Project grant no. DK29961 from the National Institutes of Health, Bethesda, Maryland and the Pathology Edu-cation Research Fund (PERF). Address reprint requests to Adriana Zeevi, PhD, Biomedical Science Tower, Rm. W1S51. University of Pittsburgh, Pittsburgh, PA 15213-2582. © 1991 by Appleton & Lange 0041-1345191/$3.00/+0 Table 1. Primed Lymphocyte Testt eel-Mediatecl Background IL-2 Response Donor Spleen Cells Lympholysis t Histology 370 ± 107 17.347 ± 513 22.141 :t 19.040 4% 174 ± 47 12.342 ± 45 12.651 ± 8.881 9% 177 ± 47 8273 ± 905 292:t 395 4% 1.093 ± 669 14.937 ± 3.464 3.964 ± 1.165 0% 65:!: 18 35.025 ± 2.779 16.097 :t 331 1% 71 :t 59 27.457 ± 3.998 296± 40 4% Jejunum 264:t 66 14.409:!:1.119 17.260 ± 1.595 51% + POD 34 Ileum 534 ± 191 26,846 ± 3.323 37.489 ± 5.201 13% + POD 34 Jejunum 273 ± 257 4.751 ± 744 367 ± 50 0% POD 55 Ileum 221 ± 208 1.771 ± 355 174:!: 67 0% POD 55 tResuIts of the PL T are expressed in counlS per minute uptake of tritiated thymidine. *The eIecIcr 10 target cell ratio was 10:1 in al assays. PeroenIage values indicaIe (5'er experimental - spontaneous reINse)/(triton total - sporIaneoua reIeae) x 100. Transplantation Proceedings. Vol 23. No 6 (December), 1991: pp O9~O944 2943 j I i 1 1 ii 1\ !Ii ,; 2944 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. RESULTS 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 alloreactive T lympho-cytes (Table 1). Follow-up biopsy at POD 55 (after solume-drol therapy) yielded neither proliferative nor cytotoxic lymphocytes. CONCLUSIONS Propagation of T cells demonstrating primed proliferative responses to donor antigens occurred nonspecifically UKNIS, ABU-ELMAGD, SUWAN ET At. throughout this patient's postoperative course_ These celIs 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 ther::.-·utic FK 506 concentrations. These cells lacked cytolytic ,apa.. bilities 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. REFERENCES I. Monchik GJ. Russell PS: Surgery 70:693. 1971 2. Hoffman AL, Makowka L. Banner B: Transplantation \9: 483, 1990 3. Todo S, Tzakis A. Abu-Elmagd K, et al: (in press) 

Functional analysis of graft lamina propria associated lymphocytes from a recipient of a human cadaveric small bowel allograft primarily immunosuppressed with FK 506

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Functional analysis of graft lamina propria associated lymphocytes from a recipient of a human cadaveric small bowel allograft primarily immunosuppressed by FK 506

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Functional analysis of graft lamina propria associated lymphocytes from a recipient of a human cadaveric small bowel allograft primarily immunosuppressed with FK 506

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