TY - JOUR
T1 - The role of protein kinase A anchoring via the RIIα regulatory subunit in the murine immune system
AU - Schillace, Robynn V.
AU - Andrews, Sarah F.
AU - Galligan, Sarah G.
AU - Burton, Kimberly A.
AU - Starks, Holly J.
AU - Bouwer, H. G.Archie
AU - McKnight, G. Stanley
AU - Davey, Michael P.
AU - Carr, Daniel W.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - Intracellular cAMP may inhibit T cell activation and proliferation via activation of the cAMP-dependent protein kinase, PKA. PKA signaling is maintained through interactions of the regulatory subunit with A-kinase anchoring proteins (AKAPs). We demonstrated that T cells contain AKAPs and now ask whether PKA anchoring to AKAPs via the RIIα regulatory subunit is necessary for cAMP-mediated inhibition of T cell activation. We studied the immune systems of mice lacking the RIIα regulatory subunit of PKA (-/-) and the ability of cells isolated from these mice to respond to cAMP. Dissection of spleen and thymus from wild-type (WT) and -/- mice, single cell suspensions generated from these organs, and iow cytometry analysis illustrate that the gross morphology, cell numbers, and cell populations in the spleen and thymus of the -/- mice are similar to WT controls. In vitro, splenocytes from -/- mice respond to anti-CD3/anti-CD28 and PMA/ionomycin stimulation and produce IL-2 similar to WT. Cytokine analysis revealed no significant difference in Th1 or Th2 differentiation. Finally, equivalent frequencies of CD8+ IFN-γ producing effector cells were stimulated upon infection of WT or -/- mice with Listeria monocytogenes. These data represent the first study of the role of RIIα in the immune system in vivo and provide evidence that T cell development, homeostasis. and the generation of a cell-mediated immune response are not altered in the RIIa -/- mice, suggesting either that RIIα is not required for normal immune function or that other proteins are able to compensate for RIIa function.
AB - Intracellular cAMP may inhibit T cell activation and proliferation via activation of the cAMP-dependent protein kinase, PKA. PKA signaling is maintained through interactions of the regulatory subunit with A-kinase anchoring proteins (AKAPs). We demonstrated that T cells contain AKAPs and now ask whether PKA anchoring to AKAPs via the RIIα regulatory subunit is necessary for cAMP-mediated inhibition of T cell activation. We studied the immune systems of mice lacking the RIIα regulatory subunit of PKA (-/-) and the ability of cells isolated from these mice to respond to cAMP. Dissection of spleen and thymus from wild-type (WT) and -/- mice, single cell suspensions generated from these organs, and iow cytometry analysis illustrate that the gross morphology, cell numbers, and cell populations in the spleen and thymus of the -/- mice are similar to WT controls. In vitro, splenocytes from -/- mice respond to anti-CD3/anti-CD28 and PMA/ionomycin stimulation and produce IL-2 similar to WT. Cytokine analysis revealed no significant difference in Th1 or Th2 differentiation. Finally, equivalent frequencies of CD8+ IFN-γ producing effector cells were stimulated upon infection of WT or -/- mice with Listeria monocytogenes. These data represent the first study of the role of RIIα in the immune system in vivo and provide evidence that T cell development, homeostasis. and the generation of a cell-mediated immune response are not altered in the RIIa -/- mice, suggesting either that RIIα is not required for normal immune function or that other proteins are able to compensate for RIIa function.
UR - http://www.scopus.com/inward/record.url?scp=18944382260&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18944382260&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.174.11.6847
DO - 10.4049/jimmunol.174.11.6847
M3 - Article
C2 - 15905526
AN - SCOPUS:18944382260
SN - 0022-1767
VL - 174
SP - 6847
EP - 6853
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -