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Science 30 July 1993:
Vol. 261. no. 5121, pp. 609 - 612
DOI: 10.1126/science.7688139
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Articles

Science, Vol 261, Issue 5121, 609-612
Copyright © 1993 by American Association for the Advancement of Science

articles

Differential T cell costimulatory requirements in CD28-deficient mice

A Shahinian, K Pfeffer, KP Lee, TM Kundig, K Kishihara, A Wakeham, K Kawai, PS Ohashi, CB Thompson, and TW Mak

Department of Medical Biophysics and Immunology, University of Toronto, Canada.

T cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. It is thought that engagement of the CD28 molecule with its ligand B7 provides an essential costimulatory signal without which full activation of T cells cannot occur. A mouse strain with a defective CD28 gene was established. Development of T and B cells in the CD28-deficient mice appeared normal. However, T lymphocytes derived from CD28-/- mutant mice had impaired responses to lectins. Lectin stimulation did not trigger interleukin-2 (IL-2) production, IL-2 receptor alpha expression was significantly decreased, and exogenous IL-2 only partially rescued the CD28 defect. Basal immunoglobulin (Ig) concentrations in CD28-deficient mice were about one-fifth of those found in wild-type controls, with low titers of IgG1 and IgG2b but an increase in IgG2a. In addition, activity of T helper cells in CD28-/- mice was reduced and immunoglobulin class switching was diminished after infection with vesicular stomatitis virus. However, cytotoxic T cells could still be induced and the mice showed delayed-type hypersensitivity after infection with lymphocytic choriomeningitis virus. Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.


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J. Biol. Chem. 279, 23394-23404
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Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis.
Y. P. de Jong, S. T. Rietdijk, W. A. Faubion, A. C. Abadia-Molina, K. Clarke, E. Mizoguchi, J. Tian, T. Delaney, S. Manning, J.-C. Gutierrez-Ramos, et al. (2004)
Int. Immunol. 16, 205-213
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CD7 and CD28 Are Required for Murine CD4+CD25+ Regulatory T Cell Homeostasis and Prevention of Thyroiditis.
G. D. Sempowski, S. J. Cross, C. S. Heinly, R. M. Scearce, and B. F. Haynes (2004)
J. Immunol. 172, 787-794
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Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells.
K. Attanavanich and J. F. Kearney (2004)
J. Immunol. 172, 803-811
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