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Human CD83 is a cell surface protein expressed predominantly by dendritic cells (DC) and lymphoid cells. So far, there exists no information on the function and distribution of mCD83. Here we demonstrate that mCD83 is moderately expressed on resting T cells and DC, but strongly increases in its expression on T cells following activation with antigenic peptides or T cell receptor-specific mAb. When returning to the resting state, T cells down-regulate CD83 again. Ig fusion proteins which express the extracellular part of the mCD83 molecule (mCD83-Ig) specifically inhibit antigen-specific T cell proliferation and IL-2 secretion in spleen cell cultures from DO11.10 T cell receptor transgenic mice. Staining of spleen cells from BALB/c, XID and mu MT (B cell) knockout mice with mCD83-Ig proteins reveals the presence of a CD83 ligand predominantly expressed most likely by B220(+) cells since spleen cells from mu MT knockout mice do not bind mCD83-Ig. CD83, besides its established expression on human dendritic cells, thus, also represents a new marker molecule on activated T cells which with its specific ligand is involved in the regulation of T cell responses.

The heat shock proteins (HSP) gp96, Hsp70 and Hsp60 activate professional antigen‐presenting cells (APC) to secrete proinflammatory cytokines and to express costimulatory molecules. Here, we analyze the impact of Hsp60 as a hypothetical danger signal on the antigen‐specific activation of T cells derived from DO11.10 TCR‐transgenic mice. The release of IFN‐γ, induced by the antigenic OVA323–339‐peptide, is increased and accelerated dramatically by the addition of Hsp60 to ex vivo purified populations of T cells and peritoneal macrophages (PEC), while the antigen‐specific IL‐2 production or proliferation of the T cells remain unchanged. In contrast, "effector" T cells, undergoing secondary stimulation, displayed almost unchanged activation kinetics in the presence of Hsp60. The presence of Hsp60 induces IFN‐γ and up‐regulation of CD69 in T cell/PEC cocultures even in the absence of antigenic peptide and this induction of IFN‐γ is strictly dependent on the ability of the macrophages to produce IL‐12. Taken together, our data strongly suggest that the presence of eukaryotic mitochondrial Hsp60 allows antigen‐specific IFN‐γ secretion under conditions when an antigenic stimulus alone is not sufficient to activate T cells.

Heat shock proteins (HSP) like Hsp60, Hsp70 and gp96 act directly on antigen-presenting cells (APC), e.g. by inducing the secretion of cytokines. Here we analyzed the impact of Hsp60 on the antigen-specific activation of CD8(+) T cells in a TCR transgenic system. Hsp60 induced low amounts of IFN-gamma in the absence of antigenic peptide; however, the release of IFN-gamma is increased by a factor of 3-10 following the addition of Hsp60 to purified populations of OT-1 [ovalbumin (OVA)257-264/H2-K(b)-restricted] T cells and antigen-pulsed peritoneal exudate cells (PEC) as APC. This effect is strictly correlated with the PEC ability to produce IL-12. In contrast, antigen-specific IL-2 secretion and T cell proliferation was not changed in the presence of Hsp60. Hsp60-containing OT-1 T cell cultures produced IFN-gamma even when the number of antigenic MHC class I complexes was too low to be stimulatory and could not be detected with specific mAb. Hsp60, thus, acts as a catalyzing molecule to initiate both innate and adaptive immune responses, and its presence (e.g. during an infection with cellular destruction) has direct consequences for the activation of otherwise 'ignorant' antigen-specific T cells.

No abstract