T(H)17 versus Treg cells in renal transplant candidates: effect of a previous transplant.
BACKGROUND
The T(H)1 and T(H)2 cells were described several years ago. However, this dichotomy has been disrupted by the description of other CD4(+) T cell subsets: the proinflammatory interleukin (IL)-17-producing T cells (T(H)17) and regulatory T cells (Tregs). The latter group inhibits the immune responses driven by T(H)1, T(H)2, and T(H)17 cells. IL-6 is involved in T(H)17 development, down-regulating Treg differentiation. Our hypothesis suggested that an imbalance between T(H)17 and Tregs enhances immune responses among renal transplant patients.


METHODS
We studied 26 end-stage renal disease (ESRD) subjects and 10 patients awaiting a second renal transplant after previous graft dysfunction. We assessed the number of CD4(+)CD25(+)Foxp3(+) cells and serum levels of IL-17, the prototypic interleukin of T(H)17 cells.


RESULTS
We observed a lower number of CD4(+)CD25(+)Foxp3(+) T cells among patients with previous graft dysfunction than those with ESRD (median 3.37 vs 8.63 cells/mm(3), P = .008). In contrast, IL-17 serum levels were augmented in graft dysfunction (median 4.45 pg/mL) compared with ESRD patients (1.39 pg/mL, P = .036), suggesting a proinflammatory state in patients awaiting a second renal transplant.


CONCLUSIONS
The emerging alloresponse from a previous transplant favors the generation of T(H)17 instead of Treg cells. The enhanced activity of T(H)17 cells in retransplanted patients may down-regulate Treg cells, producing a proinflammatory environment that favors rejection of the next transplant.
San Segundo
D
D
Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla, Fundación Marqués de Valdecilla-IFIMAV, Santander, Spain.
López-Hoyos
M
M
Fernández-Fresnedo
G
G
Benito
M J
MJ
Ruiz
J C
JC
Benito
A
A
Rodrigo
E
E
Arias
M
M
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D020381:Interleukin-17 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012086:Reoperation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit