The Journal of Immunology, Vol 155, Issue 1 118-127, Copyright © 1995 by American Association of Immunologists

ARTICLES

Antigen-presenting T cells induce the development of cytotoxic CD4+ T cells. I. Involvement of the CD80-CD28 adhesion molecules

D Mauri, T Wyss-Coray, H Gallati and WJ Pichler
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland.

The development of cytotoxic CD4+ T lymphocytes that can kill target cells in a MHC class II-restricted manner was evaluated by comparing different APCs. B-lymphoblasts (B-LCL) pulsed with the superantigen staphylococcus enterotoxin B or allogeneic B-lymphoblasts induce CD4+ T cells without cytotoxic activity. In contrast, superantigen-pulsed, MHC class II+ T cell blasts or allogeneic T cell blasts preferentially induce the development of specific, MHC class II-restricted CD4+ cytotoxic effector cells. CD4+ T cell clones generated with T or B cell blasts as APCs (T- or B-APCs) differ in their cytolytic potential, but secrete a similar cytokine pattern. Our data implicate that activated T- APCs preferentially induce a cytotoxic, CD8+ and CD4+ T cell response. Because the density of CD80 expression is lower on activated T-APCs than on B-APCs, we studied the involvement of CD28 and CD80 adhesion molecules in the generation of CD4+ CTLs. Partial blockade of the CD80 molecule with a CTLA4-Ig fusion protein and with specific anti-CD80 mAbs on B-APCs enhanced the generation of CD4+ CTLs. Specific anti-CD86 mAbs, on the contrary, had no effect on the generation of CD4+ CTLs. In contrast, stimulation of CD28, the CD80 counter-receptor, with a cross- linked B7-Ig fusion protein or with an anti-CD28 mAb, inhibited the generation of CD4+ CTLs. Thus, a reduced interaction between CD80 and CD28 may be relevant for the induction of CD4+ CTLs. This shows a new and not yet described function of these adhesion molecules. This induction of a cytotoxic immune response by T cells as APCs may be relevant for the anticlonotypic regulation of T cells and for the depletion of CD4+ T cells in HIV infection.

This article has been cited by other articles:

				E. Adamopoulou, J. Diekmann, E. Tolosa, G. Kuntz, H. Einsele, H.-G. Rammensee, and M. S. Topp Human CD4+ T Cells Displaying Viral Epitopes Elicit a Functional Virus-Specific Memory CD8+ T Cell Response J. Immunol., May 1, 2007; 178(9): 5465 - 5472. [Abstract] [Full Text] [PDF]

				M. D. Mannie, B. A. Clayson, E. J. Buskirk, J. L. DeVine, J. J. Hernandez, and D. J. Abbott IL-2/Neuroantigen Fusion Proteins as Antigen-Specific Tolerogens in Experimental Autoimmune Encephalomyelitis (EAE): Correlation of T Cell-Mediated Antigen Presentation and Tolerance Induction J. Immunol., March 1, 2007; 178(5): 2835 - 2843. [Abstract] [Full Text] [PDF]

				D. Xia, S. Hao, and J. Xiang CD8+ Cytotoxic T-APC Stimulate Central Memory CD8+ T Cell Responses via Acquired Peptide-MHC Class I Complexes and CD80 Costimulation, and IL-2 Secretion. J. Immunol., September 1, 2006; 177(5): 2976 - 2984. [Abstract] [Full Text] [PDF]

				J. Xiang, H. Huang, and Y. Liu A New Dynamic Model of CD8+ T Effector Cell Responses via CD4+ T Helper-Antigen-Presenting Cells J. Immunol., June 15, 2005; 174(12): 7497 - 7505. [Abstract] [Full Text] [PDF]

				M. D. Mannie and M. R. Walker Feedback activation of T-cell antigen-presenting cells during interactions with T-cell responders J. Leukoc. Biol., August 1, 2001; 70(2): 252 - 260. [Abstract] [Full Text] [PDF]

				A. J. McAdam, B. E. Gewurz, E. A. Farkash, and A. H. Sharpe Either B7 Costimulation or IL-2 Can Elicit Generation of Primary Alloreactive CTL J. Immunol., September 15, 2000; 165(6): 3088 - 3093. [Abstract] [Full Text] [PDF]

				L. D. Fast Recipient elimination of allogeneic lymphoid cells: donor CD4+ cells are effective alloantigen-presenting cells Blood, August 1, 2000; 96(3): 1144 - 1149. [Abstract] [Full Text] [PDF]

				D. M. Patel, P. Y. Arnold, G. A. White, J. P. Nardella, and M. D. Mannie Class II MHC/Peptide Complexes Are Released from APC and Are Acquired by T Cell Responders During Specific Antigen Recognition J. Immunol., November 15, 1999; 163(10): 5201 - 5210. [Abstract] [Full Text] [PDF]

				J. O. Brubaker, Q. Li, A. O. Tzianabos, D. L. Kasper, and R. W. Finberg Mitogenic Activity of Purified Capsular Polysaccharide A from Bacteroides fragilis: Differential Stimulatory Effect on Mouse and Rat Lymphocytes In Vitro J. Immunol., February 15, 1999; 162(4): 2235 - 2242. [Abstract] [Full Text] [PDF]

				M. Battifora, G. Pesce, F. Paolieri, N. Fiorino, C. Giordano, A. M. Riccio, G. Torre, D. Olive, and M. Bagnasco B7.1 Costimulatory Molecule Is Expressed on Thyroid Follicular Cells in Hashimoto's Thyroiditis, But Not in Graves' Disease J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 4130 - 4139. [Abstract] [Full Text]

				G. G. Bashian, C. M. Braun, S.-K. Huang, A. Kagey-Sobotka, L. M. Lichtenstein, and D. M. Essayan Differential Regulation of Human, Antigen-specific Th1 and Th2 Responses by the B-7 Homologues, CD80 and CD86 Am. J. Respir. Cell Mol. Biol., August 1, 1997; 17(2): 235 - 242. [Abstract] [Full Text]