MHC class II biosynthesis by activated rat CD4+ T cells: development of repression in vitro and modulation by APC-derived signals.
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.
Mannie
Mark D
MD
Department of Microbiology and Immunology, Brody Medical Sciences Building, East Carolina University School of Medicine, Greenville, NC 27834, USA. manniem@mail.ecu.edu
Dawkins
John G
JG
Walker
Mindi R
MR
Clayson
Barbara A
BA
Patel
Dhaval M
DM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D003208:Concanavalin A