Molecular characterization of U937-dependent T-cell co-stimulation.
Journal: 1999/July - Immunology
ISSN: 0019-2805
PUBMED: 10233676
Abstract:
U937 cells provide a co-stimulatory signal for CD3-mediated T-cell activation which is independent of the CD28/CD80/CD86 interaction. This study set out to identify which molecules contribute to this co-stimulatory activity. Monoclonal antibodies (mAb) to the known accessory molecules CD11a, CD18, CD54 and CD45, all inhibited T-cell proliferation. Although CD11a/18 mAb inhibited U937/T-cell cluster formation as well as proliferation, CD45 enhanced the size of the clusters formed, suggesting that this was not the only mechanism of inhibition. The alternative co-stimulatory pathway provided by U937 cells preferentially stimulated a response in the CD18+ T-cell population, and this reflected the reduced sensitivity of CD8+ T cells to CD28-mediated activation. Monoclonal antibodies to three molecules, CD53, CD98 and CD147, also inhibited U937-dependent T-cell proliferation. The mAb to CD98 and CD147 were inhibitory when prepulsed on to the U937 cells, suggesting an effect mediated by these molecules on the antigen-presenting cell.
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Immunology 96(1): 35-47

Molecular characterization of U937-dependent T-cell co-stimulation

Department of Immunology, Windeyer Institute of Medical Sciences, University College London, London, UK
Correspondence: Professor D. R. Katz, Department of Immunology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London W1P 6DB, UK.
Department of Immunology, Windeyer Institute of Medical Sciences, University College London, London, UK
Received 1998 May 5; Revised 1998 Sep 21; Accepted 1998 Sep 24.

Abstract

U937 cells provide a co-stimulatory signal for CD3-mediated T-cell activation which is independent of the CD28/CD80/CD86 interaction. This study set out to identify which molecules contribute to this co-stimulatory activity. Monoclonal antibodies (mAb) to the known accessory molecules CD11a, CD18, CD54 and CD45, all inhibited T-cell proliferation. Although CD11a/18 mAb inhibited U937/T-cell cluster formation as well as proliferation, CD45 enhanced the size of the clusters formed, suggesting that this was not the only mechanism of inhibition. The alternative co-stimulatory pathway provided by U937 cells preferentially stimulated a response in the CD18 T-cell population, and this reflected the reduced sensitivity of CD8 T cells to CD28-mediated activation. Monoclonal antibodies to three molecules, CD53, CD98 and CD147, also inhibited U937-dependent T-cell proliferation. The mAb to CD98 and CD147 were inhibitory when prepulsed on to the U937 cells, suggesting an effect mediated by these molecules on the antigen-presenting cell.

Abstract

Acknowledgments

This work was supported by a UK MRC PhD studentship (T.J.S.), a grant from the Sir Jules Thorn Charitable Trust (V.E.W.), a Shanks fellowship (P.S.H.), a Wellcome Trust vacation studentship (H.A.) and a grant from the UK Multiple Sclerosis Society (M.G.). The kind gift of monoclonal antibodies from Drs A.J. van Agthoven, G.Aversa, D. A. Fox, D. L. Hardie, A. J. Henniker, V. Horejsi, W. Knapp, Y. van Kooyk, K. Sagawa, D. C. Shen, K. M. Skubitz, D. C. Shen, H. Taskov, R. Vilella, and the organizers of the relevant mAb panels for the 6th HLDA is gratefully acknowledged.

Acknowledgments

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