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 profess ional antigen-presenting cells (APC) on T cell proliferation, cytokine prod uction and surface molecule expression. Ag presentation by T cells (T-T pre sentation) induced an initial T cell activation phase as measured by prolif eration and IL-2 production. These activated T cells became anergic upon an tigenic restimulation by professional APC, as shown by a failure to prolife rate or produce IL-2 or IFN-gamma. Interestingly, such T cells were not int rinsically defective in their signal transduction pathways since they did p roliferate and produce cytokines upon restimulation with mitogenic stimuli. Flow cytometric analysis revealed a more profound TCR and CD3 down-regulat ion 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 d uring T-T presentation or subsequent antigenic restimulation of anergic T c ells in the presence of professional APC, whereas increased expression of t hese molecules was observed during professional APC-T presentation of non-a nergic T cells. The impaired expression of costimulatory and activation mol ecules on T cells after T-T presentation of Ag might lead to altered intera ctions between T cells and professional APC upon antigenic restimulation. W e propose that T cell anergy is a functional consequence of these altered T cell-APC interactions.