Kidney transplant patients with long-term graft survival have altered expression of molecules associated with T-cell activation.
BACKGROUND
Patients with long-term functioning organ allografts may have developed different mechanisms that explain the lack of graft rejection. However, it is not known how these mechanisms interplay or whether one of them predominates in such situations.


METHODS
The authors analyzed the expression of T-cell surface molecules involved in alloantigen recognition, signal transduction, co-stimulation, and activation markers on circulating T cells from patients with normal kidney function 10 or more years after transplantation, short-term survival (1-4 years), and chronic rejection and from healthy adults. The percentage and the median fluorescent intensity of each marker were determined by flow cytometry. Proliferative response against specific and third-party donors and mitogenic stimulation were also determined.


RESULTS
Peripheral blood lymphocytes from patients with long-term surviving kidneys had decreased expression of T-cell receptor (TCR)-alphabeta (P < 0.01), CD3epsilon (P < 0.05), and CD3 zeta-chains (P < 0.001); diminished percentages of CD4(+)CD28(+) (P < 0.001) cells; and increased expression of CTLA-4(+) (P < 0.01) on CD3(+) cells. CD4(+)CD25(+)CD69(+) cells were also increased in long-term surviving patients. Long-term surviving patients had decreased donor-specific proliferative responses.


CONCLUSIONS
The decreased expression of TCR-alphabeta and epsilon- and zeta-chains on circulating T cells of long-term surviving patients suggests that these cells may have defects in alloantigen recognition or signal transduction that may result in decreased numbers of T cells expressing co-stimulatory molecules and activation markers as well as a decreased specific proliferative response. The decrease in the percentage of CD28(+) cells and the increase in CD4(+)CD25(+)CD69(+) cells suggest that regulatory mechanisms of the immune response are still active in such patients.
Alvarez
Cristiam M
CM
Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia.
Paris
Sara C
SC
Arango
Liliana
L
Arbelaez
Mario
M
Garcia
Luis F
LF
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell