title: CD4+CD25+Foxp3+ indirect alloreactive T cells from renal transplant patients suppress both the direct and indirect pathways of allorecognition.
abstract: Alloreactive T cells recognize donor antigens by two routes: direct and indirect pathways of allorecognition. Although the direct pathway is reported to be dominant in allograft rejection, indirect allorecognition also plays an important role. Indirect alloreactivity is also observed in renal transplant patients irrespective of rejection. Previously we showed a predominance of interleukin (IL)-10 induced by indirect allorecognition of donor human leucocyte antigen (HLA)-DR peptides, suggesting the existence of indirect alloreactive T cells displaying regulatory activity. In the present work, our objective was to characterize these regulatory T cells. We detected indirect alloproliferation of peripheral blood mononuclear cells (PBMC) from renal transplant patients, induced by donor HLA-DR peptides, dependent on IL-4 or IL-10, suggesting regulatory activity as part of the alloreactive T-cell repertoire. PBMC-derived indirect alloreactive T-cell lines were established and produced both inflammatory and regulatory cytokines. We showed that two of these T-cell lines which were able to inhibit both direct and indirect alloproliferation of another T-cell line from the same patient presented a CD4(+)CD25(+)Foxp3(+) T-cell population. These data support the idea that indirect alloreactive T cells may also have regulatory activity and may contribute to the maintenance of the human renal allograft.
authors.affiliation: Heart Institute (InCor), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Spadafora-Ferreira
authors.forename: C
authors.initials: C
authors.lastname: Caldas
authors.forename: K C
authors.initials: KC
authors.lastname: Faé
authors.forename: I
authors.initials: I
authors.lastname: Marrero
authors.forename: S M
authors.initials: SM
authors.lastname: Monteiro
authors.forename: H T
authors.initials: HT
authors.lastname: Lin-Wang
authors.forename: A
authors.initials: A
authors.lastname: Socorro-Silva
authors.forename: S G
authors.initials: SG
authors.lastname: Fonseca
authors.forename: J A
authors.initials: JA
authors.lastname: Fonseca
authors.forename: J
authors.initials: J
authors.lastname: Kalil
authors.forename: V
authors.initials: V
authors.lastname: Coelho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D017634:Self Tolerance / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors