Allospecific CD154+ T cells identify rejection-prone recipients after pediatric small-bowel transplantation.
BACKGROUND
Up to 70% of children with small bowel transplantation (SBTx) experience acute cellular rejection (ACR). Allospecific CD154+ T cells predict liver ACR in children in a novel, 16-hour mixed leukocyte response (MLR) assay, but remain untested in SBTx.


METHODS
The expression of CD154 was measured in 4 subsets-naive (N) and memory (M) CD154+ T-helper (Th) and T-cytotoxic (Tc) cells (ie, CD154+ ThN, CD154+ ThM, CD154+ TcN, and CD154+ TcM, respectively)-in the MLR of single blood samples obtained from 32 children with SBTx within 60 days of SBTx biopsy. Children showing ACR in these biopsies were termed Rejectors. The ratio of donor-induced to third-party-induced CD154+ T cells was called the immunoreactivity index (IR). We hypothesized that IR >1 denoted increased donor-specific alloreactivity and increased risk of rejection; in contrast, IR <1 implied decreased risk. CD154 expression was correlated with the expression of CTLA4, a negative T-cell costimulator that antagonizes and is inversely related to CD154 (n = 18).


RESULTS
Rejectors showed significantly greater numbers of donor-specific CD154+ T-cell subsets. Logistic regression analysis and leave-one-out cross validation followed by receiver operating characteristic analysis showed that, among the 4 subsets, IR > or =1.23 for CD154+ TcM identified Rejectors with a sensitivity and specificity of 93% and 88%. Also, a significant negative correlation was observed between CD154 expression and CTLA4 expression in allospecific Tc (Spearman's rho = -0.616, P = .006) but not in Th.


CONCLUSIONS
Allospecific CD154+ TcM identify rejection-prone children with SBTx.
Ashokkumar
Chethan
C
Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.
Gupta
Ankit
A
Sun
Qing
Q
Ningappa
Mylarappa B
MB
Higgs
Brandon W
BW
Mazariegos
George
G
Fazzolare
Tamara
T
Remaley
Lisa
L
Soltys
Kyle
K
Bond
Geoffrey
G
Abu-Elmagd
Kareem
K
Sindhi
Rakesh
R
D023201:CD40 Ligand / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007421:Intestine, Small / Q000637:transplantation*; D007519:Isoantigens / Q000032:analysis*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D016176:T-Lymphocyte Subsets; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D007519:Isoantigens; D023201:CD40 Ligand; D016559:Tacrolimus