AbstractUsing anin vitroantigenic stimulation model of murine spleen cells in the presence of the immunosuppressor cyclosporin A (CSA) we have previously reported that not only does this drug not interfere with the differentiation of T lymphocytes into memory cells it appears to favor this differentiation (Motta, I. et al.,Eur. J. Immunol.1991. 21: 551). Because CSA blocks interleukin‐2 (IL‐2) gene expression, we have analyzed the effect of this cytokine on memory T helper cell development. Murine splenic cells were primed for 6 days with sheep red blood cells (SRBC) in protocols in which either IL‐2 was not produced or its biological activity was neutralized by anti‐IL‐2 receptor (R) antibodies. The helper function of the recovered T cells was revealed by their capacity to help virgin B splenocytes produce anti‐SRBC antibodies upon challengein vitro.We found that CD4+cells primed in the absence of IL‐2, provoked either by IL‐2 gene transcription blockade by CSA or by treatment with anti‐IL‐2R antibodies, afford the best helper functions. These cells exhibit a memory‐type phenotype characterized by the low expression of the MEL‐14 marker and the high expression of the CD44 marker. Evidence is also presented that memory T helper cells originate in part from naive subset displaying the MEL‐14hiphenotype. The pattern of expression of the genes encoding different cytokines (IL‐2, IL‐4, IL‐5 and interferon‐γ) following a secondary antigenic stimulation shows that the helper function of the cells primed in the absence of IL‐2 correlates with the upregulation of the IL‐2 and the IL‐5 genes. From these data, we conclude that IL‐2 plays a major role in the
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