Distinct requirements for C-C chemokine and IL-2 production by naive, previously activated, and anergic T cells

Ag presented by activated APCs promote inmunogenic responses whereas Ag pre sented by resting APCs leads to tolerance. In such a model, the regulation of cytokine release by the presence or absence of costimulation might poten tially play a critical role in dictating the ultimate outcome of Ag recogni tion, C-C chemokines are a structurally defined family of chemoattractants that have diverse effects on inflammation. We were interested in determinin g the activation requirements for chemokine production by CD4(+) T cells. O ur data demonstrate for T cell clones and previously activated T cells from TCR-transgenic mice that stimulation with anti-TCR alone results in the pr oduction of copious amounts of macrophage-inflammatory protein-1 alpha (MIP -1 alpha) and other C-C chemokines, and that addition of anti-CD28 gives ve ry little augmentation. Furthermore, MIP-1 alpha production is nearly equiv alent from both anergic and nonanergic cells. For naive T cells, anti-CD3 s timulation alone led to as much MIP-1 alpha production as Ag + APC stimulat ion, The addition of costimulation gave a 3-10-fold enhancement, but this w as 70-fold less than the effect of costimulation on IL-2 production. Thus, although C-C chemokines play a broad role in influencing inflammation, thei r production by signal 1 alone makes them unlikely to play a critical role in the decision between a tolerogenic and an immunogenic response, Furtherm ore, the production of MIP-1 alpha by anergic T cells, as well as following signal 1 alone, raises the possibility that in vivo this chemokine serves to recruit activated T cells to become tolerant.