Few studies have addressed the consequences of physical interactions between NK and T cells, as well as physical interactions among NK cells themselves. We show in this study that NK cells can enhance T cell activation and proliferation in response to CD3 cross-linking and specific Ag through interactions between 2B4 (CD244) on NK cells and CD48 on T cells. Furthermore, 2B4/CD48 interactions between NK cells also enhanced proliferation of NK cells in response to IL-2. Overall, these results suggest that NK cells augment the proliferation of neighboring T and NK cells through direct cell-cell contact. These results provide new insights into NK cell-mediated control of innate and adaptive immunity and demonstrate that receptor/ligand-specific cross talk between lymphocytes may occur in settings other than T-B cell or T-T cell interactions.

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.

CD83 is a marker molecule for mature dendritic cells (DCs) but is also substantially expressed on activated T cells in humans and mice. Its function is unknown, but CD83 knockout mice show an impaired thymic maturation of CD4-positive cells and soluble CD83 inhibits partially antigen-specific responses in vitro pointing to a role of CD83 in the immune system. Here we show that CD83-positive T cells produce strongly increased amounts of interferon-g and interleukin-2. In contrast, constitutive expression of CD83 on DCs alters neither the activation of DCs following addition of lipopolysaccharide nor the ability to present antigenic peptides. Thus, the expression of CD83 on T cells has direct functional consequences for tuning the activation threshold.

SUMMARYIFN-g, produced after infection with Trypanosoma cruzi, has been shown to be crucial in the determination of resistance or susceptibility. We have performed a detailed study on the expression of IFN-g and of the IFN-g-inducing cytokines IL-12 and IFN-g-inducing factor (IGIF)/IL-18 with regard to time course and tissue localization. IFN-g was present in high amounts in the serum and in the supernatants of unseparated spleen cells and isolated CD4þ and CD8 þ T cells from the spleens of infected mice which were stimulated ex vivo with T. cruzi. Using the in situ hybridization technique we demonstrate that IL-12 p40 messages were expressed in the spleen and increased during infection, correlating with the expression of IFN-g transcripts. Furthermore, we show for the first time that the mRNA for the cytokine IL-18 was induced by a parasitic infection and that this expression increased during infection with T. cruzi. Interestingly, the message for IL-18 was produced earlier during infection and already had declined until day 38, when IFN-g and IL-12 p40 transcripts were optimally expressed. Surprisingly, the changes in IL-12 and IL-18 mRNA production were clearly seen only by in situ hybridization, but less clearly by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). This is possibly due to the extensive activation and proliferation of spleen cells observed during infection leading to a dilution of these specific mRNAs.

CD83 is used as a marker for mature dendritic cells (DC) in man. We have developed a new monoclonal antibody (mAb), Michel-17, that specifically recognizes mouse CD83. We show that murine CD83 is expressed mainly on mature DC and on activated T cells. Histological analysis of serial spleen sections revealed a CD83 expression pattern resembling that of MIDC-8, a known murine DC marker molecule. In contrast to other costimulatory receptors, cross-linking of CD83 with the mAb Michel-17 on DC or T cells does not induce any activation signals. Our data describe for the first time the expression pattern of murine CD83, which is comparable to that of human CD83. The unique mAb Michel-17 will help to elucidate the biological functions of the CD83 molecule in more detail.