Elena Gubina

Assignment1 of DLK1 to human chromosome band 14q32 by in situ hybridization

DLK1 (delta [Drosophila]-like 1) encodes dlk, a transmembrane protein member of the EGF-like homeotic family. Members of this family participate in cell-to-cell interactions that control cell fate during differentiation. The dlk protein contains six EGF-like repeats in its extracellular domain that are highly homologous to similar domains of the Drosophila protein Delta (Laborda et al., 1993) and other EGF-like homeotic protein family members. dlk also contains a unique transmembrane domain and a short intracellular region. pG2, FA-1 (Fetal Antigen 1), Pref-1 (Preadipocyte factor 1), and dlk have all been shown to be identical or polymorphic products of a single gene (Lee et al., 1995). dlk has also been called SCP-1 (stromal cell derived protein 1) and ZOG protein (Halder et al., 1998). The functional importance of dlk in the control of cellular differentiation has been shown in several cell types, including small cell lung cancer cell lines (Laborda et al., 1993), preadipocytes (Smas and Sul, 1993), immune stem cells (Moore et al., 1997) hematopoietic stromal cells and B lymphocytes (Bauer et al., 1998), and adrenal glomerulosa cells (Halder et al., 1998). Chromosome mapping of this gene may be important to explore whether gene deletion or duplication may be associated with diseases or defaults in embryonic development. Materials and methods

ICAM‐1 enhances MHC‐peptide activation of CD8+ T cells without an organized immunological synapse

In addition to the TCR‐ligand interaction, other receptor‐ligand pairs, such as LFA‐1 and ICAM‐1, play a major role in the activation of T cells. Recent studies of T cell activation suggest a coordinated movement of LFA‐1 and ICAM‐1 in forming a defined zone in the immunological synapse. It is unclear from these studies whether the organized molecular geometry of the immunological synapse is necessary for ICAM‐1 enhancement of T cell activation. In this report, we demonstrate that ICAM‐1 can enhance the activation of CD8+ T cells by MHC‐peptide in the absence of an organized immunologic synapse. Therefore, although the molecular organization of the immunologic synapse may amplify stimuli, it is not an absolute requirement for either CD8+ T cell activation or the ICAM‐1 enhancement of TCR activation.

Organ-Specific Cytokine Polarization Induced by Adoptive Transfer of Transgenic T Cells

There are two distinct phenotypes of T cell cytokine responses that lead to different effector functions and different outcomes in disease processes. Although evidence suggests a possible role of the local microenvironment in the differentiation or localization of T cells with these phenotypes, there are no examples of divergent T cell cytokine phenotypes with the same Ag specificity concurrently existing in different tissue compartments. Using a CD8+ T cell adoptive transfer model for graft-vs-host disease, we demonstrate that a potent type 2 cytokine response develops in the spleen while a potent type 1 cytokine response simultaneously develops in the testis. These experiments demonstrate for the first time that cytokine production can be oppositely polarized in different organs of the same individual. This may have important implications for organ-specific pathology in infection or autoimmunity: infections or autoimmune diseases that affect multiple organs may have heterogeneity in tissue cytokine responses that is not revealed in systemic lymphocyte cytokine responses. Therefore, attempts to modulate the immune response phenotype may ameliorate pathology in one organ while exacerbating pathology in another.

Assignment of dlk (Dlk1) to mouse chromosome band 12E–F1 by in situ hybridization

The dlk (Delta-like) gene (Dlk1) encodes a transmembrane protein member of the EGF-like homeotic family. Members of this family participate in cell-to-cell interactions that control cell fate during differentiation. Dlk is a transmembrane protein, with a short intracellular tail, that contains in its extracellular domain six EGF-like repeats highly homologous to similar domains of the Drosophila proteins Notch, Delta and Serrate (Laborda et al., 1993) and other EGF-like homeotic protein family members. Pref-1 (Preadipocyte factor 1), FA-1 (Fetal Antigen 1), and dlk have all been shown to be identical or polymorphic products of a single gene (Lee et al., 1995). This gene has been also named SCP-1 (stromal cell derived protein 1) and ZOG (Halder et al., 1998). The functional importance of dlk in the control of cellular differentiation has been shown in several cell types, including small cell lung cancer cell lines (Laborda et al., 1993), preadipocytes (Smas and Sul, 1993), (Garcés et al., 1999) immune stem cells (Moore et al., 1997) hematopoietic stromal cells and B lymphocytes (Bauer et al., 1998), and adrenal glomerulosa cells (Halder et al., 1998). Mapping of the human counterpart of the dlk gene has been performed (Gubina et al, 1999) and the gene localized to 14q32. We now report localization of the mouse gene in a homologous chromosome region. Chromosome mapping of this gene may be important to explore whether gene deletion or duplication may be associated with diseases or defaults in embryonic development in mouse or humans. Fig. 1 . FISH mapping of the mouse dlk gene with probe 12280. The specific signals detected on chromosome 12 are indicated by arrows. The specificity of the localization was confirmed by co-hybridization with a biotin labeled probe specific for the centromere of chromosome 12. Observation of specifically labeled chromosomes 12 demonstrated that Dlk1 is located at band 12E–F1. The picture was generated by Genome System Inc.