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Evidence of Alternative or Concomitant Use of Perforin- and Fas-Dependent Pathways in a T Cell-Mediated Negative Regulation of Ig Production¹

Unité d’Immunophysiologie Moléculaire, Institut Pasteur, Paris, France

To study the possible involvement of perforin (Pfp)- and/or Fas-dependent cytotoxicity pathways in a T cell-mediated negative regulation of Ig production, we used the T cell-induced Ig-allotype suppression model. T splenocytes from Igh^a/a mice, when neonatally transferred into histocompatible Igh^a/b F₁ or Igh^b/b congenic hosts, are intrinsically able to totally, specifically, and chronically suppress the production of IgG_2a of the Igh^b haplotype (IgG_2a^b). It has not been established whether the suppression effectors, which are anti-IgG_2a^b MHC class I-restricted CD8⁺ T cells, cytolyse IgG_2a^b+ B targets or whether they only silence Ig production. In this study, using T cells from Igh^a/a Pfp^+/+ or Pfp^o/o mice, the latter obtained by crossbreeding, and B cells from Igh^b/b Fas^+/+ or Fas^lpr/lpr (lymphoproliferation) mice in appropriate adoptive transfer models, we demonstrated that: 1) under blockage of the Pfp-mediated pathway, Igh^a/a T cells were still able to induce suppression against wild-type IgG_2a^b+ B cells, 2) IgG_2a^b+ B cells with impaired Fas expression were also subjected to suppression by WT Igh^a/a T splenocytes, and 3) the suppression establishment was totally inhibited when both Pfp- and Fas-dependent mechanisms were simultaneously blocked, i.e., when Igh^a/a Pfp^o/o T cells were used to induce suppression against Igh^b/b Fas^lpr/lpr B cells. These results provide the first demonstration of the existence of alternative or simultaneous use of the major cytotoxic mechanisms in a T cell-mediated down-regulation of an Ig production.

This article has been cited by other articles:

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				L. Majlessi and G. Bordenave Non-overlapping Fas- and BCL-2-regulated death pathways in IgG2ab-producing B cells Int. Immunol., July 1, 2000; 12(7): 969 - 976. [Abstract] [Full Text] [PDF]