Regulating T helper cell immunity through antigen responsiveness and calcium entry.
We evaluated changes in the signaling potentials and proliferative capacity of single antigen-specific T helper (TH) cells during a primary immune response to a protein antigen. At the peak of cellular expansion in vivo all antigen-specific TH cells exhibited a profound block in CD3- and CD4-mediated mobilization of intracellular calcium together with a more global block in T cell receptor-independent capacitative calcium entry (CCE). The proliferative response of these antigen-specific TH cells to anti-CD3, anti-CD28 and IL-2 was also severely blunted. Cross-linking CD69 on a substantial fraction of CD69+ antigen-specific TH cells relieved this block in CCE and restored proliferative capacity in vitro. The CCE rescue operated through a CD69-coupled G protein and required calcium-bound calmodulin and calcineurin. These data reveal critical changes in the responsiveness of antigen-specific TH cells and provide evidence of new mechanisms for the regulation of antigen-specific TH cell development in vivo.
Bikah
G
G
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Pogue-Caley
R R
RR
McHeyzer-Williams
L J
LJ
McHeyzer-Williams
M G
MG
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D020013:Calcium Signaling; D002147:Calmodulin / Q000378:metabolism; D002455:Cell Division; D010856:Columbidae; D003432:Cross-Linking Reagents; D003574:Cytochrome c Group / Q000276:immunology; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000099192:CD69 Antigens
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D019703:Calcineurin; D002147:Calmodulin; D003432:Cross-Linking Reagents; D003574:Cytochrome c Group; D019204:GTP-Binding Proteins; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens