title: A low effective dose of interleukin-7 is sufficient to maintain cord blood T cells alive without potentiating allo-immune responses.
abstract: Slow reconstitution of T cell immunity remains a critical issue after umbilical cord blood (CB) transplantation. Although this may be a consequence of the low cell dose, it may also reflect the propensity of naïve T cells, which predominate in CB, to undergo apoptotic cell death. Exogenous interleukin 7 (IL-7) can prevent apoptosis of naïve T cells, but at high concentrations, IL-7 may also expand alloreactive T cells, thereby aggravating the risk of graft-versus-host disease. We evaluated the survival of CB T cells from 34 healthy full-term pregnancies, and we found wide interdonor variation, from 17.4% to 79.7%, of CB T cells that were still alive after being rested for 4 days in culture medium without cytokine supplementation. The viability of CB T cells was negatively correlated to infant birth weight (Spearman's ρ = .376; P = .031) and positively correlated to venous CB pH (ρ = .397; P = .027); both associations were confirmed by multivariate analysis (P = .023 and P = .005, respectively). A low supplemental concentration (100 pg/mL) of recombinant human IL-7 was sufficient to maintain the viability of cryopreserved/thawed CB T cells, with most (>80%) cells remaining in a quiescent state and without significant changes in their CD4/CD8 ratio and the proportion of CD4(+) CD31(+) PTK7(+) recent thymic emigrants. IL-7 at 100 pg/mL did not lead to any significant enhancement of the alloreactive response of CB T cells, as evaluated by proliferation rates (thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester dilution) and interferon-gamma production (ELISPOT). This effective concentration of IL-7 is far lower than that obtained in vivo after pharmacological administration of the cytokine. This study suggests that administration of lower doses of recombinant human IL-7 than used in previous clinical trials may be sufficient to sustain the viability of infused CB T cells and, thus, help to accelerate naïve T cell reconstitution without potentiating their alloreactivity.
authors: Service d'Onco-hématologie, Université Catholique de Lille, Lille, France; EA2686, Université Lille Nord de France, UDSL Faculté de Médecine, Laboratoire d'Immunologie HLA, CHRU de Lille, Lille, France.
authors: Laurent
authors: L
authors: Pascal
authors: UAM Allogreffe de CSH, CHRU de Lille, Lille, France.
authors: Bénédicte
authors: B
authors: Hivert
authors: EA2686, Université Lille Nord de France, UDSL Faculté de Médecine, Laboratoire d'Immunologie HLA, CHRU de Lille, Lille, France.
authors: Jacques
authors: J
authors: Trauet
authors: UAM Allogreffe de CSH, CHRU de Lille, Lille, France.
authors: Eva
authors: E
authors: Deberranger
authors: EA2686, Université Lille Nord de France, UDSL Faculté de Médecine, Laboratoire d'Immunologie HLA, CHRU de Lille, Lille, France.
authors: Jean-Paul
authors: JP
authors: Dessaint
authors: EA2686, Université Lille Nord de France, UDSL Faculté de Médecine, Laboratoire d'Immunologie HLA, CHRU de Lille, Lille, France; UAM Allogreffe de CSH, CHRU de Lille, Lille, France.
authors: Ibrahim
authors: I
authors: Yakoub-Agha
authors: EA2686, Université Lille Nord de France, UDSL Faculté de Médecine, Laboratoire d'Immunologie HLA, CHRU de Lille, Lille, France. Electronic address: myriam.labalette@chru-lille.fr.
authors: Myriam
authors: M
authors: Labalette
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000494:pharmacology*; D017710:Lymphocyte Transfusion; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: C508605:IL7 protein, human; D015851:Interleukin-7
keywords: Alloreactivity; Cord blood T cells; Interleukin-7