title: Proliferative alloresponse of T cytotoxic cells identifies rejection-prone children with small bowel transplantation.
abstract: BACKGROUND
  More than 60% children with small bowel transplantation (SBTx) experience acute cellular rejection.
  
  
  OBJECTIVE
  To identify children at risk of rejection, donor- and third-party-induced proliferation of T-helper and T cytotoxic (Tc) cells, and their naïve 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 (CFSE(low)) 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 CFSE(low) 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 CFSE(low) 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.
authors.affiliation: Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Chethan
authors.initials: C
authors.lastname: Ashokkumar
authors.forename: Ankit
authors.initials: A
authors.lastname: Gupta
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Brandon W
authors.initials: BW
authors.lastname: Higgs
authors.forename: Mylarappa
authors.initials: M
authors.lastname: Ningappa
authors.forename: Sara
authors.initials: S
authors.lastname: Snyder
authors.forename: Matthew
authors.initials: M
authors.lastname: Johnson
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.forename: Kyle
authors.initials: K
authors.lastname: Soltys
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bond
authors.forename: Kareem
authors.initials: K
authors.lastname: Abu-Elmagd
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sindhi
mesh_terms: D000208:Acute Disease; D000818:Animals; D002455:Cell Division; D002675:Child, Preschool; D018920:Coculture Techniques; D005434:Flow Cytometry; D005916:Globulins; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007223:Infant; D007421:Intestine, Small / Q000473:pathology / Q000637:transplantation*; D007959:Lymphocyte Culture Test, Mixed; D011817:Rabbits; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D005916:Globulins