A role for interleukin-12 in the regulation of T cell plasma membrane compartmentation.
The immunological synapse initiates the clustering and stabilization of the T cell receptor by the formation of a large lipid microdomain that accumulates (e.g. CD4/CD8) and segregates (e.g. CD45 and LFA-1) some proteins of the T cell plasma membrane. This work shows that a fraction of transmembrane glycoproteins CD26 and CD45 (the R0 isoform in particular) is present in the rafts of fresh and activated human T lymphocytes. CD26 is proposed as the costimulator of TCR-dependent activation, and CD45 is essential to the T cell activation process because it dephosphorylates at least the inhibitory site of Src kinases. These findings support a more complex model of compartmentation, depending on the stage of T cell maturation and post-transcriptional and post-translational regulation. In addition, interleukin 12 (IL-12; inducer of TH1 responses) drives CD26 and CD45R0 to particular microdomains, thereby involving interleukins in the rules governing raft inclusion or exclusion. The physical association of CD26 and CD45R0 has long been reported. The results presented in this work fit a model in which IL-12 up-regulates a certain type of CD26 expression that interacts on the cell surface with CD45R0, near but outside of the raft core. The use of antisense oligonucleotides for the CD26 mRNAs demonstrated that both events (enhanced by IL-12), CD26-CD45R0 association and membrane compartment redistribution, are related. Thus, CD26 could be part of a shuttling mechanism for CD45 that regulates membrane tyrosine-phosphatase activities, e.g. to control IL-12 receptor-dependent signal transduction.
Salgado
Francisco J
FJ
Department of Biochemistry and Molecular Biology, Universidade de Santiago de Compostela, Spain.
Lojo
Juan
J
Alonso-Lebrero
José Luis
JL
Lluis
Carmen
C
Franco
Rafael
R
Cordero
Oscar J
OJ
Nogueira
Montserrat
M
D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure
D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D017493:Leukocyte Common Antigens; D018819:Dipeptidyl Peptidase 4