International Immunology, Vol. 11, No. 5, 667-675,
May 1999
© 1999 Japanese Society for Immunology
Phenotypic analysis of CTLA-4 and CD28 expression during transient peptide-induced T cell activation in vivo
Department of Pathology and Microbiology, University of Bristol School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
Correspondence to: B. Metzler
The T cell co-stimulatory receptors CD28 and CTLA-4 appear to have opposite effects on T cell activation, mediating augmentation and inhibition of T cell 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 expression has a major impact on the regulation of immune responses. While the kinetics of co-stimulatory molecules have been established for T cell stimulation in vitro, little is known about CD28 and CTLA-4 expression in response to T cell activation in vivo. In this study we have investigated the kinetics of CD28 and CTLA-4 expression upon CD4+ T cell activation in response to soluble peptide in vivo. Using mice transgenic for a T cell receptor specific for the I-Au-restricted N-terminal peptide of myelin basic protein 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. Administration 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 expressing CTLA-4, CD25 and CD45RBlow was identified in mice that had not been treated with specific peptide. The implications of these observations for immune regulation are discussed.
Keywords: CD28, CTLA-4, phenotypic analysis, T cell activation
1 Present address: Howard Hughes Medical Institute, Cancer Research Laboratory, Department of Molecular and Cell Biology, 415 Life Sciences Addition, University of California, Berkeley, CA 94720, USA
Transmitting editor: J. P. Allison
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