Antigen presentation by T cells versus professional antigen-presenting cells (APC): differential consequences for T cell activation and subsequent T cell-APC interactions.
We compared the effects of antigen (Ag) presentation by T cells and professional antigen-presenting cells (APC) on T cell proliferation, cytokine production and surface molecule expression. Ag presentation by T cells (T-T presentation) induced an initial T cell activation phase as measured by proliferation and IL-2 production. These activated T cells became anergic upon antigenic restimulation by professional APC, as shown by a failure to proliferate or produce IL-2 or IFN-gamma. Interestingly, such T cells were not intrinsically defective in their signal transduction pathways since they did proliferate and produce cytokines upon restimulation with mitogenic stimuli. Flow cytometric analysis revealed a more profound TCR and CD3 down-regulation during T-T presentation than during APC-T presentation. However, no up-regulation of CD80, CD86, CD45RC and OX40 (CD134) was observed on T cells during T-T presentation or subsequent antigenic restimulation of anergic T cells in the presence of professional APC, whereas increased expression of these molecules was observed during professional APC-T presentation of non-anergic T cells. The impaired expression of co-stimulatory and activation molecules on T cells after T-T presentation of Ag might lead to altered interactions between T cells and professional APC upon antigenic restimulation. We propose that T cell anergy is a functional consequence of these altered T cell-APC interactions.
Taams
L S
LS
Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
van Eden
W
W
Wauben
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002455:Cell Division; D017635:Clonal Anergy / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2