Interleukin-2 down-modulates memory T helper lymphocyte development during antigenic stimulation in vitro.
Using an in vitro antigenic 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 challenge in 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-14hi phenotype. The pattern of expression of the genes encoding different cytokines (IL-2, IL-4, IL-5 and interferon-gamma) following a secondary antigenic stimulation shows that the helper function of the cells primed in the absence of IL-2 correlates with the up-regulation of the IL-2 and the IL-5 genes. From these data, we conclude that IL-2 plays a major role in the control of memory T helper cell induction.
Bemer
V
V
Unité d'Immunophysiologie Moléculaire, Institut Pasteur, Paris, France.
Motta
I
I
Perret
R
R
Truffa-Bachi
P
P
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000187:drug effects*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D019041:L-Selectin / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012756:Sheep; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D019041:L-Selectin; D016572:Cyclosporine