Leona P. Whichard

Characterization of human thymic epithelial cell surface antigens: Phenotypic similarity of thymic epithelial cells to epidermal keratinocytes

Cellular interactions between developing thymocytes and cells of the thymic microenvironment are necessary for maturation of thymocytes into mature T cells. While much is known about the molecules on developing T cells that mediate these interactions, little is known about the surface molecules of human thymic epithelial (TE) cells. In this study, using a panel of 276 MAb including 255 MAb from the 5th International Workshop on Human Leukocyte Differentiation Antigens (HLDA-V), we have determined the expression of CD1 through CDw130 and other surface molecules on resting and IFN-γ-activated cultured human TE cells and on resting epidermal keratinocytes (EK). We demonstrate the surface expression of 50 of the 161 molecules assayed for on TE cells, including a number of adhesion molecules, cytokine receptors,Apo-1, and MHC-encoded molecules. While activation of TE cells with IFN-γ for 48 hr induced a greater than fivefold increase in the expression of four surface molecules (CD38, CD54, MHC class I, and MHC class II), it also induced a greater than 50% increase in the expression of 14 other surface molecules (CD12, CD29, CD40, CD44, CD47, CD49b, CD49c, CD49e, CD55, CD66, CD87, CD104, TE4, and STE3) and a decrease in the expression of three molecules (CDw65, CDw109, and STE2). In comparing the phenotype of TE cells to 83 other cell lines studied in HLDA-V, we found that TE cells were strikingly more similar to EK than to any of the other cell types tested.

Cytokine-regulated expression of activated leukocyte cell adhesion molecule (CD166) on monocyte-lineage cells and in rheumatoid arthritis synovium

OBJECTIVE To determine whether monocyte/macrophage expression of the CD6 ligand, activated leukocyte cell adhesion molecule (ALCAM) (CD166), is regulated by cytokines during inflammation in rheumatoid arthritis (RA). METHODS We used flow cytometry to test whether cytokines present in rheumatoid synovium could regulate ALCAM cell surface expression on peripheral blood (PB) monocytes and RA synovial fluid (SF) macrophages, and we examined ALCAM expression in situ in RA synovium by immunofluorescence. RESULTS The monocyte differentiation factors interleukin-3, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor augmented ALCAM expression on PB monocytes. ALCAM was expressed on monocyte-lineage cells in situ in inflamed synovium from patients with RA (9 of 9), but not in uninflamed synovium from patients with joint trauma (0 of 3). Furthermore, in vitro culture-induced ALCAM expression on PB monocytes and CD14+ RA SF cells was inhibited by an M-CSF neutralizing antibody. CONCLUSION ALCAM expression on PB and SF monocytes/macrophages is enhanced by M-CSF.

Thymocytes and cultured thymic epithelial cells express transcripts encoding α-3, α-5 and β-4 subunits of neuronal nicotinic acetylcholine receptors: preferential transcription of the α-3 and β-4 genes by immature CD4+8+ thymocytes

Thymic tissues express transcripts encoding the alpha-3, alpha-5 and beta-4 subunits of nicotinic neuronal acetylcholine receptors (AcChRs) suggesting that neuronal AcChRs similar to those expressed in ganglia are expressed in the thymus. Transcription occurs in both isolated thymocytes and thymic epithelial cells. RT-PCR analyses of thymocyte subsets indicate that immature CD4 + 8 + thymocytes express higher levels of the alpha-3 and beta-4 transcripts than more mature thymocytes. Compared to freshly isolated thymocytes, peripheral blood lymphocytes do not express alpha-3 and beta-4 AcChR subunit transcripts. Cultured thymocytes rapidly down-regulate transcription of the alpha-3 and beta-4 AcChR subunit genes by a process that is not reversed by stimulation with phytohemagglutinin and IL-2. Thus our results indicate that there is transcriptional regulation of neuronal AcChR subunit genes during the process of thymocyte maturation and that factors within the thymic microenvironment influence expression of the alpha-3 and beta-4 AcChR subunit genes by developing T cells.