Expansion Of Cd4+cd7-T Cells, A Memory Subset With Preferential Interleukin-4 Production, After Bone Marrow Transplantation

Abstract

Inadequate reconstitution of CD4+ lymphocyte and interleukin (IL)-2 production defect are observed after bone marrow or peripheral blood stem cell transplantation (SCT).We studied immune reconstitution after SCT in 33 consecutive patients who received allogeneic SCT (17 patients) or autologous SCT (16 patients). The aims were to assess the regeneration of the CD4+ T-cell subset with regard to helper cell differentiation. CD4+ T-cell subset regeneration and expansion of the CD4+CD7- subset were studied by immunofluorescence analysis. CD4+CD7- cell cytokine secretion was analyzed after cell sorting and costimulation of the CD3 and CD28 pathways, in enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction assays.We report a relative expansion of the CD4+CD7- subset within CD4+ T cells, detected as early as 1 month after bone marrow transplantation and decreasing after day 60. CD4+CD7- T cells preferentially expressed CD45RO and activation markers such as CD57, CD25, and HLA-DR. No relationship was observed between the CD4+CD7- expansion and transplant-related complications. We observed no significant IL-2 production in supernatants from sorted CD4+CD7- T cells, whereas IL-4 levels were comparable to those produced by cells from normal individuals. Autologous CD4+CD7+ cells showed little, if any, IL-4 production, and IL-2 production was lower than that by normal CD4+CD7+ T cells. Reverse transcription-polymerase chain reaction assays showed similar amounts of interferon-gamma transcripts in the two subsets; tumor necrosis factor-alpha, IL-4, and IL-10 transcripts were detected in CD4+CD7- T cells but not in their CD4+CD7+ counterparts.These data confirm the IL-2 production defect after bone marrow transplantation and suggest that the CD4+CD7- T-cell subset might be preferentially involved in the enhanced production of IL-4 and low production of IL-2. These data show that the early immune reconstitution in CD4+ T cells after SCT preferentially involves memory T cells with a Th0/Th2 differentiation that might participate in the T-helper cell defect.