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Proliferative Alloresponse of T Cytotoxic Cells Identifies Rejection-Prone Children With Small Bowel Transplantation

  作者 Ashokkumar, C; Gupta, A; Sun, Q; Higgs, BW; Ningappa, M; Snyder, S; Johnson, M; Mazariegos, G; Soltys, K; Bond, G; Abu-Elmagd, K; Sindhi, R  
  选自 期刊  Transplantation;  卷期  2010年89-11;  页码  1371-1377  
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[摘要]Background. More than 60% children with small bowel transplantation (SBTx) experience acute cellular rejection.Purpose/Methods. To identify children at risk of rejection, donor-and third-party-induced proliferation of T-helper and T cytotoxic (Tc) cells, and their naive and memory (M) subsets was evaluated simultaneously in single blood samples from 28 children who received SBTx after induction with rabbit anti-human thymocyte globulin. Proliferation was measured by dilution of the intravital dye carboxyfluorescein succinimidyl ester (CFSE) in 3- to 4-day mixed leukocyte reaction co-culture. The ratio of donor-and third-party-induced proliferation (CFSElow) of the T cells was reported as the immunoreactivity (IR) index for each subset. Rejectors were defined as those who experienced biopsy-proven acute cellular rejection within 60 days of the assay. IR more than 1 signified increased risk of rejection and IR less than 1 implied decreased risk.Results. Rejectors (n = 16) and Nonrejectors (n = 12) were similar in general demographics. Significantly higher counts were observed for all proliferated CFSElow T-cell subsets among rejectors, compared with nonrejectors. Logistic regression, leave-one-out cross-validation, and receiver operating characteristic analyses showed that the IR of Tc associated best with biopsy-proven rejection (sensitivity >87.5%, specificity >83.3%). IR of CFSElow Tc correlated significantly with IR of proinflammatory, allospecific CD154(+) Tc-M (r = 0.682, P = 0.005) and inversely with IR of allospecific, antiinflammatory, CTLA4(+) Tc-M (r = -0.638, P = 0.047).Conclusions. Proliferative alloresponses of Tc cells can identify rejection-prone children receiving SBTx.

 
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