The Journal of Immunology, Vol 145, Issue 1 85-93, Copyright © 1990 by American Association of Immunologists

ARTICLES

Costimulatory requirements of murine Th1 clones. The role of accessory cell-derived signals in responses to anti-CD3 antibody

IR Williams and ER Unanue
Department of Pathology, Washington University, School of Medicine, St. Louis, MO 63110.

We examined the role of accessory cell-derived signals in promoting growth and lymphokine production by murine Th1 clones. Five of six Th1 clones failed to proliferate to immobilized anti-CD3 antibody despite producing IL-2 and IFN-gamma. These clones became unresponsive to Ag after exposure to anti-CD3. With the addition of irradiated splenic accessory cells (SAC), Th1 clones proliferated to anti-CD3 and produced greater amounts of IL-2 and IFN-gamma. High doses of plate-bound anti- CD3 completely inhibited responses of these clones to IL-2 and diminished the growth-promoting activity of SAC. The costimulatory effects of SAC on growth of Th1 clones were also seen in the presence of exogenous IL-2, indicating that enhanced IL-2 production alone was not responsible for the costimulatory effect. Delivery of the costimulatory signal from SAC required their close proximity to the T cells. The costimulatory activity of SAC was not reproduced by the addition of IL-1, IL-6, or IL-1 plus IL-6. IL-7 induced weak proliferation of Th1 clones, but did not synergize with plate-bound anti-CD3. Our results suggest a model in which SAC-derived costimulatory signals regulate growth of Th1 cells primarily at the level of cell cycle progression rather than at the level of IL-2 production.

This article has been cited by other articles:

				H. M. Ashour and T. M. Seif The role of B cells in the induction of peripheral T cell tolerance J. Leukoc. Biol., November 1, 2007; 82(5): 1033 - 1039. [Full Text] [PDF]

				D.-G. Lim, K. Bieganowska Bourcier, G. J. Freeman, and D. A. Hafler Examination of CD8+ T Cell Function in Humans Using MHC Class I Tetramers: Similar Cytotoxicity but Variable Proliferation and Cytokine Production Among Different Clonal CD8+ T Cells Specific to a Single Viral Epitope J. Immunol., December 1, 2000; 165(11): 6214 - 6220. [Abstract] [Full Text] [PDF]

				H. Dooms, T. Van Belle, M. Desmedt, P. Rottiers, and J. Grooten Interleukin-15 redirects the outcome of a tolerizing T-cell stimulus from apoptosis to anergy Blood, August 1, 2000; 96(3): 1006 - 1012. [Abstract] [Full Text] [PDF]

				A. Inoue, C.-S. Koh, M. Yamazaki, and H. Yagita Effect of Anti-B7-1 and Anti-B7-2 mAb on Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease J. Immunol., December 1, 1999; 163(11): 6180 - 6186. [Abstract] [Full Text] [PDF]

				J. N. Agrewala, S. Suvas, R. K. Verma, and G. C. Mishra Differential Effect of Anti-B7-1 and Anti-M150 Antibodies in Restricting the Delivery of Costimulatory Signals from B Cells and Macrophages J. Immunol., February 1, 1998; 160(3): 1067 - 1077. [Abstract] [Full Text] [PDF]

				G. Freeman, F Borriello, R. Hodes, H Reiser, K. Hathcock, G Laszlo, A. McKnight, J Kim, L Du, D. Lombard, et al. Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice Science, November 5, 1993; 262(5135): 907 - 909. [Abstract] [PDF]