Rapid T cell receptor modulation accompanies lack of in vitro mitogenic responsiveness of double negative T cells to anti-CD3 monoclonal antibody in MRL/Mp-lpr mice.
The role of the CD8-, CD4- (double negative) (DN) T cells accumulating in MRL/Mp-lpr/lpr (lpr) mice is unclear. Although they bear the TCR/CD3, the lpr DN cells do not respond to Ag, and the specificity of TCR/CD3 on these cells is unknown. With the aid of monoclonal anti-murine CD3 epsilon (145-2C11), we have investigated the function of the CD3 molecule on the DN cells. 145-2C11 was not mitogenic for lpr DN lymph node cells (LNC), even in the presence of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, whereas MRL/Mp-+/+ (+/+) LNC responded strongly. Surprisingly, CD3 modulation induced by 145-2C11 was much more rapid for lpr DN than for +/+ LNC. For example, the modulation observed after 10 min in lpr DN LNC required at least 2 h in +/+ cells. This was not due solely to a property of the 145-2C11 antibody, because both TPA and the F23.1 anti-TCR mAb also provoked a faster modulation of the TCR in lpr DN LNC. Double-staining experiments showed that co-culturing +/+ and lpr DN LNC did not alter their respective rates of modulation, which suggests an intrinsic defect in the lpr DN cells. Moreover, in LNC from 6-wk-old lpr mice (before the appearance of DN cells), as well as in normal phenotype-bearing T cells (CD8+ or CD4+) from 6-mo-old lpr mice, the CD3 modulation was similar to that of +/+ LNC. After modulation, the CD3 molecule was reexpressed at the surface of both +/+ and lpr DN cells during subsequent incubation of the cells without 145-2C11. In addition, spontaneous recycling of CD3 was similar in +/+ and lpr DN LNC. The rapid modulation of the lpr DN TCR/CD3 is presumably related to the anergy of this cell population.
Davignon
J L
JL
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D002453:Cell Cycle; D005434:Flow Cytometry; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D013755:Tetradecanoylphorbol Acetate