Intragraft Th17 infiltrate promotes lymphoid neogenesis and hastens clinical chronic rejection.
To evaluate the influence of intragraft inflammatory infiltrate on the course of chronic rejection, 11 human renal grafts, detransplanted for terminal failure, were analyzed. Samples were divided into two groups according to their graft survival (> or < or = 8 y). In both groups, the main cell population infiltrating the graft interstitia was T lymphocytes. The extent of the lymphocytic infiltration and the distribution of naive and memory, CD4(+) and CD8(+) T cells, were similar in both groups. Although all types of Th polarization profiles can lead to terminal chronic rejection, a correlation between shorter graft survival and the presence of Th17 cells that produce IL-17 and IL-21 was observed. In contrast, grafts infiltrated by regulatory T cells survived significantly longer. The correlation between the expressions of activation-induced cytidine deaminase (the key enzyme of the germinal center reaction) and IL-21 suggests that Th17 could exert their deleterious effect by promoting lymphoid neogenesis, namely, the organization of inflammatory effectors into ectopic germinal centers in which a local humoral immune response is elicited. Further studies will determine whether Th17 infiltration can be used as a prognosis tool and whether the Th17 subset constitutes a therapeutic target for slowing down chronic rejection.
Deteix
Clémence
C
Université Lyon 1, Villeurbanne, France.
Attuil-Audenis
Valérie
V
Duthey
Aurélie
A
Patey
Natacha
N
McGregor
Brigitte
B
Dubois
Valérie
V
Caligiuri
Giuseppina
G
Graff-Dubois
Stéphanie
S
Morelon
Emmanuel
E
Thaunat
Olivier
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002675:Child, Preschool; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D018836:Inflammation Mediators; D020381:Interleukin-17