Toso, a functional IgM receptor, is regulated by IL-2 in T and NK cells.
We find that the cell surface receptor Toso is dramatically downregulated by in vitro stimulation of human T and NK cells with IL-2 in a STAT5-dependent manner. The fact that IL-2 is known to prime NK and T cells for Fas/TNF-mediated activation-induced cell death (AICD) fits nicely with the original and recent descriptions of Toso as an inhibitor of Fas/TNF-induced apoptosis. In support of this possibility, effector memory T cells express markedly lower levels of Toso than those of naive T cells, indicating that activation in vivo correlates with the downregulation of Toso. Moreover, in vitro activation of memory T cells through TCR dramatically downregulates Toso expression compared with that of naive CD4 T cells. However, overexpression of Toso in human NK cells and Jurkat T cells does not inhibit Fas-mediated apoptosis, and, in agreement with other recent reports, Toso clearly functions as an IgM receptor. Unlike CD16, Toso expression by NK cells does not convey cytotoxic potential, but its ligation does trigger intracellular signaling in NK cells. In summary, our data indicate that Toso is a functional IgM receptor that is capable of activating signaling molecules, is regulated by IL-2, and is not inherently an antiapoptotic molecule.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Yousuke
Y
Murakami
Sriram
S
Narayanan
Su
S
Su
Richard
R
Childs
Konrad
K
Krzewski
Francisco
F
Borrego
Jennifer
J
Weck
John E
JE
Coligan
D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C491901:FAS protein, human; C112037:FCMR protein, human; D007376:Interleukin-2; D008565:Membrane Proteins; D011961:Receptors, Fc; D019014:fas Receptor; C035311:immunoglobulin M receptor