T cell activation through Thy-1 is associated with the expression of a surface protein (p100) on a subset of CD4 cells.
Thy-1 molecules, which lack a transmembrane domain, can nonetheless induce T cell activation; it has thus been suggested that a separate transmembrane molecule associated with Thy-1 is required for signal transduction. We have previously characterized a transmembrane protein with an Mr of 100,000 (p100), which is non-covalently bound to two glycosyl-phosphatidylinositol (GPI)-linked molecules, Thy-1 and ThB. p100 is selectively expressed on the T cell surface and divides peripheral CD4 cells into two subpopulations. This differential expression on CD4 cells allowed us to investigate the role of p100 in signal transduction through Thy-1 molecules. Here we report that only p100+ CD4 cells proliferate and release cytokines in response to cross-linkage of Thy-1, although both p100+ and p100- CD4 cells strongly express Thy-1 on their surfaces. Control stimulation by anti-CD3 antibodies or concanavalin A induces identical thymidine uptake by the two CD4 cell populations. Interestingly, these two populations of CD4 cells had different cytokine release profiles after activation through CD3: only p100+ CD4 cells released high amounts of IL-2 and IFN-gamma, whereas both populations released IL-4. p100 expression correlates with the induction of homotypic aggregation of T cells after Thy-1 triggering. p100 is associated with kinase activity (fyn and lck), and phosphorylated proteins of 90, 59, 57 and 33 kDa co-precipitate with Thy-1 only in p100+ CD4 cells. Altogether, these data suggest that p100 is involved in signal transduction through Thy-1. p100 expression by activated CD4 cells in vivo may be relevant to the proposed function of Thy-1 as an accessory signaling molecule in cell activation.
Lehuen
A
A
Institut National de la Santé et de la Recherche Médicale, Hôpital Necker, Paris, France.
Beaudoin
L
L
Bernard
M
M
Kearney
J F
JF
Bach
J F
JF
Monteiro
R C
RC
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002449:Cell Aggregation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011494:Protein Kinases / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000276:immunology / Q000502:physiology*
D000954:Antigens, Surface; D016207:Cytokines; D008565:Membrane Proteins; D018800:Thy-1 Antigens; D011494:Protein Kinases