Distinct Requirements for C-C Chemokine and IL-2 Production by Naive, Previously Activated, and Anergic T Cells

Abstract

Ag presented by activated APCs promote immunogenic responses whereas Ag presented by resting APCs leads to tolerance. In such a model, the regulation of cytokine release by the presence or absence of costimulation might potentially play a critical role in dictating the ultimate outcome of Ag recognition. C-C chemokines are a structurally defined family of chemoattractants that have diverse effects on inflammation. We were interested in determining the activation requirements for chemokine production by CD4+ T cells. Our data demonstrate for T cell clones and previously activated T cells from TCR-transgenic mice that stimulation with anti-TCR alone results in the production of copious amounts of macrophage-inflammatory protein-1α (MIP-1α) and other C-C chemokines, and that addition of anti-CD28 gives very little augmentation. Furthermore, MIP-1α production is nearly equivalent from both anergic and nonanergic cells. For naive T cells, anti-CD3 stimulation alone led to as much MIP-1α production as Ag + APC stimulation. The addition of costimulation gave a 3–10-fold enhancement, but this was 70-fold less than the effect of costimulation on IL-2 production. Thus, although C-C chemokines play a broad role in influencing inflammation, their production by signal 1 alone makes them unlikely to play a critical role in the decision between a tolerogenic and an immunogenic response. Furthermore, the production of MIP-1α 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.

CD47 Signaling Regulates the Immunosuppressive Activity of VEGF in T Cells

“…TSP1 signaling via CD47 inhibits TCR signaling, including induction of the early activation marker CD69 (28, 33, 42). Consistent with the previous report that VEGF inhibits T cell activation (19), VEGF treatment resulted in a 4-fold reduction in CD69 mRNA expression induced by activation of WT Jurkat T cells in the presence of anti-CD3+CD28 for 24 h (Fig.…”

Chemokines and Antitumor Immunity: Walking the Tightrope

“…Although the role of tumor-derived CCL3 and CCL4 in antitumor immunity has not been well delineated, a recent report concerning CCL3 may warrant further investigation. Lerner et al [90] reported that CCL3 was secreted by T cells stimulated with signal one in the absence of signal two and accordingly may play a role in T cell tolerance. As a result, it is interesting to speculate that tumor-derived CCL3 may play a role in tumor-induced immune tolerance.…”

Rainbow trout (Oncorhynchus mykiss) sIgM− leucocytes secrete an interleukin-2 like growth factor after mitogenic stimulation in vitro

“…The benefit of monoclonal antibodies (mabs) against surface receptors for separating those leucocyte subpopulations was shown earlier using panning techniques [20] or immunomagnetic separation [22]. In the present study sIgM leucocytes (sIgM T lymphocytes, NK cells and thrombocytes) depleted from sIgM + B lymphocytes using two mabs against trout IgM were used to characterise growth factors which were secreted by sIgM leucocytes after mitogenic stimulation into culture supernatants (conditioned media, CM), a well known phenomena of activated mammalian T lymphocytes [29,30]. For an optimal detection of secreted molecules in PAGE and Westernblot a serum-free cultivation systems was used.…”