MHC class II biosynthesis by activated rat CD4+ T cells: development of repression in vitro and modulation by...

This study focused on synthesis of MHC class II glycoproteins (MHCII) by rat CD4(+) T-helper cells. During activation in Con A and IL-2, purified rat splenic CD4(+) T cells expressed abundant surface MHCII together with transcripts for I-A alpha/beta, invariant chain, and the type III and type IV MHC class II transactivator (CIITA). Activated thymic CD8(+)CD4(-) and CD8(+)CD4(+) T cells exhibited essentially the same phenotype. MHCII synthesis by CD4(+) T cells enabled presentation of myelin basic protein (MBP) to antigen-specific responders. T cell expression of MHCII was due to direct biosynthesis rather than adsorption from professional APC; indeed, T cell-mediated expression of MHCII was optimal in the absence of professional APC. Despite periodic reactivation with Con A during 3-4 weeks of culture, CD4(+) T cells repressed MHCII synthesis and reverted to a MHCII(-) phenotype. These short-term lines resembled established lines of MBP-specific T cells in that mitogenic activation elicited extensive blastogenesis without MHCII synthesis. Activation-dependent synthesis of MHCII however was partially restored in lines of mitogen-stimulated T cells when the cultures were reconstituted with irradiated splenic APC. These data indicate that most naive rat CD4(+) T cells exhibit activation-dependent synthesis of MHCII whereas continuously propagated T cells require an APC-derived signal to support MHCII synthesis.