B. Metzler et al., Phenotypic analysis of CTLA-4 and CD28 expression during transient peptide-induced T cell activation in vivo, INT IMMUNOL, 11(5), 1999, pp. 667-675
The T cell co-stimulatory receptors CD28 and CTLA-4 appear to have opposite
effects an T cell activation, mediating augmentation and inhibition of T c
ell responses respectively. Since these two receptors use the same ligands,
CD80 (B7-1) and CD86 (B7-2), the co-ordinate timing of CD28 and CTLA-4 exp
ression has a major impact on the regulation of immune responses. While the
kinetics of co-stimulatory molecules have been established for T cell stim
ulation in vitro, little is known about CD28 and CTLA-4 expression in respo
nse to T cell activation in vivo. In this study we have investigated the ki
netics of CD28 and CTLA-4 expression upon CD4(+) T cell activation in respo
nse to soluble peptide in vivo. Using mice transgenic for a T cell receptor
specific for the I-A(u)-restricted N-terminal peptide of myelin basic prot
ein MBP Ac1-9, we show maximal up-regulation of both CD28 and CTLA-4 2 days
after peptide administration. CTLA-4 expression correlated positively with
early activation markers on the same cells and was high on blast cells. Ad
ministration of peptide analogs with higher affinity for I-AU MHC class II
revealed a higher increase in CTLA-4 than in CD28 expression in response to
improved TCR ligation, Further, a small population of CD4(+) T cells expre
ssing CTLA-4, CD25 and CD45RB(low) was identified in mice that had not been
treated with specific peptide. The implications of these observations for
immune regulation are discussed.