PKCtheta signals activation versus tolerance in vivo.
Understanding the pathways that signal T cell tolerance versus activation is key to regulating immunity. Previous studies have linked CD28 and protein kinase C-theta (PKCtheta) as a potential signaling pathway that influences T cell activation. Therefore, we have compared the responses of T cells deficient for CD28 and PKCtheta in vivo and in vitro. Here, we demonstrate that the absence of PKCtheta leads to the induction of T cell anergy, with a phenotype that is comparable to the absence of CD28. Further experiments examined whether PKCtheta triggered other CD28-dependent responses. Our data show that CD4 T cell-B cell cooperation is dependent on CD28 but not PKCtheta, whereas CD28 costimulatory signals that augment proliferation can be uncoupled from signals that regulate anergy. Therefore, PKCtheta relays a defined subset of CD28 signals during T cell activation and is critical for the induction of activation versus tolerance in vivo.
Berg-Brown
Nancy N
NN
Ontario Cancer Institute, University Health Network, 610 University Ave., Toronto, M5G 2M9 Canada.
Gronski
Matthew A
MA
Jones
Russell G
RG
Elford
Alisha R
AR
Deenick
Elissa K
EK
Odermatt
Bernhard
B
Littman
Dan R
DR
Ohashi
Pamela S
PS
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism*; D015704:CD4 Antigens / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus
D018106:CD28 Antigens; D015704:CD4 Antigens; D007527:Isoenzymes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta