The Journal of Immunology, Vol 141, Issue 6 1848-1854, Copyright © 1988 by American Association of Immunologists

ARTICLES

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

JL Davignon, PL Cohen and RA Eisenberg
Department of Medicine, University of North Carolina, Chapel Hill 27599.

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.

This article has been cited by other articles:

				A. R. A. Hamad, A. Srikrishnan, P. Mirmonsef, C. P.M. Broeren, C. H. June, D. Pardoll, and J. P. Schneck Lack of Coreceptor Allows Survival of Chronically Stimulated Double-negative {alpha}/{beta} T Cells: Implications for Autoimmunity J. Exp. Med., May 14, 2001; 193(10): 1113 - 1122. [Abstract] [Full Text] [PDF]