Down-modulation of CD2 delays deletion of superantigen-responsive T cells.
CD2 is a cell surface glycoprotein expressed on most T lymphocytes that is generally viewed as a cell adhesion molecule and, in this capacity, contributes to T cell receptor (TCR) signaling. CD2 has a relatively long cytoplasmic tail which associates with the src family tyrosine kinases, p56(lck) and p59(fyn), and could potentially signal directly. Down-modulation of CD2 on T cells has been shown to result in diminished proliferative capacity and interleukin (IL)-2 production. Furthermore, re-expression of CD2 can result in the restoration of these functions. This suggests that CD2 can influence the intensity of TCR signaling. As TCR signal intensity is pivotal to the induction of T cell apoptosis, we considered the hypothesis that the level of CD2 on the T cell surface may influence its propensity toward apoptosis. Using an anti-CD2 antibody, CD2 was down-modulated in vivo on mouse T lymphocytes without affecting the levels of surface CD3, TCR alphabeta, CD4 or CD8. Deletion of superantigen-responsive T cells was delayed in mice with down-modulated CD2 following the administration of staphylococcal enterotoxin B (SEB). This was paralleled by diminished apoptosis of SEB-responsive cells. The findings suggest a model whereby the level of CD2 expression influences the intensity of TCR signaling and the ability to undergo apoptosis.
Fortner
K A
KA
Department of Medicine, The University of Vermont College of Medicine, Burlington 05405-0068, USA.
Russell
J Q
JQ
Budd
R C
RC
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis; D018801:CD2 Antigens / Q000096:biosynthesis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D017637:Clonal Deletion; D015536:Down-Regulation / Q000187:drug effects*; D004768:Enterotoxins / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects; D018089:Superantigens / Q000276:immunology*
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D018801:CD2 Antigens; D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; C031818:enterotoxin B, staphylococcal