IL-7 induces surface expression of B7/BB1 on pre-B cells and an associated increase in their costimulatory effects on T cell proliferation.
Treatment with IL-7 of NALM-6 pre-B cells, but not of EBV-LCL, Daudi, HeLa, or K562 cells resulted in enhanced costimulatory activity for TSST-1-induced T cell proliferation. The effect of IL-7 on the costimulatory function of NALM-6 cells was dose-dependent, could be inhibited by a neutralizing anti-IL-7 mAb, and resulted in the need of less costimulatory cells, or less superantigen, to obtain proper T cell proliferation. Addition of anti-IL-7 mAb to the coculture of superantigen-stimulated T cells with IL-7-pretreated NALM-6 cells did not alter the T cell responses obtained without addition of this antibody. These findings suggest that a possible costimulation of T cells by surface-bound IL-7 on pretreated NALM-6 cells did not contribute to the enhanced costimulatory function observed. Rather, these studies implicate IL-7-induced alterations of the NALM-6 cells themselves as the basis for the enhanced costimulatory activity observed. The most remarkable phenotypic differences between efficient costimulatory B lineage cells and deficient pre-B cells are a lower expression of ICAM-1 (CD54) and a lack of expression of the costimulatory B cell activation antigen B7/BB1. Upon activation with IL-7, the expression of ICAM-1 was increased, and the expression of B7/BB1 antigens was induced. The increased T cell responses in the presence of IL-7-treated NALM-6 cells could be inhibited by addition of anti-BB1 mAb. These results suggest that B7/BB1-negative pre-B cells may acquire the surface expression of B7/BB1 upon stimulation with IL-7, a process which is associated with increased costimulatory function for T cell proliferation.
Dennig
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Sloan-Kettering Institute, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
O'Reilly
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RJ
D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D015851:Interleukin-7