September 3, 2003 (Journal of Clinical Investigation) -- The differentiation of naive T cells into memory T cells is a crucial step in the evolution of an immune response. Optimal activation requires 2 steps: (i) T cell receptor binding to the foreign antigen; and (ii) engagement of the CD28 molecule on the T cell with it's ligands on the antigen presenting cell - a process known as costimulation. In contrast with naοve T cells, memory T cells can be activated after engagement of the T cell receptor, without CD28-mediated costimulation.
Andrew Fontenot and colleagues at the University of Colorado Health Sciences Center studied the role of CD28 costimulation in patients with chronic beryllium disease (CBD). These individuals suffer from granulomatous inflammation of the lung resulting from continued exposure to beryllium in the workplace. The authors found that although the majority of T cells in peripheral blood from patients with CBD are CD28+, a large fraction of the CD4+ T cells that accumulate in the lung are CD28-. Despite the absence of CD28 costimulation, these cells are able to mount an immune response. However, upon comparison with CD28+ cells they have a reduced ability to proliferate and are more susceptible to cell death upon exposure to foreign antigen.
The data support a model in which central memory CD4 cells maintain dependence on CD28 stimulation while cells accumulating in the periphery in response to chronic engagement with beryllium become progressively functionally independent of CD28, and then lose CD28 expression. This is associated with a decline in the ability of these cells to survive and proliferate.
The study lends great insight into the maintenance of memory cells and their persistence at the site of chronic inflammatory disease.
