Homeostatic T Cell Proliferation after Islet Transplantation

Figure 1

A model comparison of antigen driven versus homeostatic T cell proliferation. In conditions of immune competence and steady-state circulating lymphocyte counts, T cell proliferation can occur in an antigen-specific manner. MHC-peptide antigen complex is recognized by a specific T cell receptor on the T cell surface. Antigen-activated T cells express CD25 and produce IL-2 in an autocrine manner. Low levels of IL-7 are necessary for T cell survival. Reduction of T cell number is accompanied by increased IL-7. Proliferation of T cells relies on homeostatic mechanisms. T cells express the IL-7 receptor stimulated by supraphysiological levels of IL-7. Proliferation is antigen and co-stimulation independent and generated effector cells with characteristics that are remarkably similar to those of antigen expanded T cells. All immunosuppressive drugs inhibit antigen-specific T cell proliferation. In contrast, during homeostatic proliferation only MMF can inhibit T cell expansion, whereas cyclosporine A, FK506, and rapamycin have no effect and anti-CD25 monoclonal promotes IL-7 mediated proliferation.