The Journal of Immunology, Vol 142, Issue 6 1929-1936, Copyright © 1989 by American Association of Immunologists

ARTICLES

Tumor necrosis factor synergistically acts with IFN-gamma to regulate Ly-6A/E expression in T lymphocytes, thymocytes and bone marrow cells

TR Malek, KM Danis and EK Codias
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.

The Ly-6 alloantigens represent a family of phosphatidylinositol anchored proteins that function in the process of T lymphocyte activation and whose expression are often induced on T and B lymphocytes after activation by mitogens or Ag. Previous studies have shown that the induction of Ly-6 alloantigens in T cells is at least in part due to the action of IFN-alpha/beta or IFN-gamma. In the present report, we have demonstrated that IFN-gamma also induced Ly-6 molecules on B lymphocytes, several B cell tumors, and bone marrow cells. Furthermore, we now show that TNF also participates in the induction of at least one of the Ly-6 proteins, Ly-6A/E. TNF was found to synergize with IFN-gamma to induce Ly-6A/E expression in thymocytes, T lymphocytes, bone marrow cells, but not B lymphocytes. For T lymphocytes, the synergistic induction of Ly-6A/E by TNF was restricted to cells from the Ly-6.1 haplotype, whereas IFN-gamma was sufficient to fully induce Ly-6A/E expression in cells from the Ly-6.2 haplotype. This result is consistent with the notion that there is more complex regulation of the Ly-6A/E molecules in T cells obtained from the Ly-6.1 haplotype. For T lymphocytes from BALB/c (Ly-6.1) mice, Ly-6A/E, but not Ly-6C, molecules were synergistically induced by IFN-gamma and TNF. The induction of Ly-6A/E molecules on BALB/c T cells resulted in an enhanced capacity to activate these cells through the Ly-6 T cell activation pathway. One transformed T cell line, 5.1.2, was also identified whose Ly-6A/E molecules were synergistically induced by IFN- gamma and TNF. Optimal expression of Ly-6A/E molecules on 5.1.2 cells required continuous culture of this cell line with these two cytokines and resulted in the detection of optimal levels of cytoplasmic Ly-6A/E mRNA by Northern blot analysis. This latter result suggests that IFN- gamma and TNF regulate Ly-6A/E at the level of transcription and/or mRNA stabilization.

This article has been cited by other articles:

				G. Grenier, A. Scime, F. Le Grand, A. Asakura, C. Perez-Iratxeta, M. A. Andrade-Navarro, P. A. Labosky, and M. A. Rudnicki Resident Endothelial Precursors in Muscle, Adipose, and Dermis Contribute to Postnatal Vasculogenesis Stem Cells, December 1, 2007; 25(12): 3101 - 3110. [Abstract] [Full Text] [PDF]

				C. Tso, G. Martinic, W.-H. Fan, C. Rogers, K.-A. Rye, and P. J. Barter High-Density Lipoproteins Enhance Progenitor-Mediated Endothelium Repair in Mice Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1144 - 1149. [Abstract] [Full Text] [PDF]

				L. Yang, J. J. Kobie, and T. R. Mosmann CD73 and Ly-6A/E Distinguish In Vivo Primed but Uncommitted Mouse CD4 T Cells from Type 1 or Type 2 Effector Cells J. Immunol., November 15, 2005; 175(10): 6458 - 6464. [Abstract] [Full Text] [PDF]

				N. Sizemore, A. Agarwal, K. Das, N. Lerner, M. Sulak, S. Rani, R. Ransohoff, D. Shultz, and G. R. Stark Inhibitor of {kappa}B kinase is required to activate a subset of interferon {gamma}-stimulated genes PNAS, May 25, 2004; 101(21): 7994 - 7998. [Abstract] [Full Text] [PDF]

				C. Y. Ito, C. Y. J. Li, A. Bernstein, J. E. Dick, and W. L. Stanford Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A-null mice Blood, January 15, 2003; 101(2): 517 - 523. [Abstract] [Full Text] [PDF]

				B. K. al-Ramadi, M. H. Al-Dhaheri, N. Mustafa, M. AbouHaidar, D. Xu, F. Y. Liew, M. L. Lukic, and M. J. Fernandez-Cabezudo Influence of Vector-Encoded Cytokines on Anti-Salmonella Immunity: Divergent Effects of Interleukin-2 and Tumor Necrosis Factor Alpha Infect. Immun., June 1, 2001; 69(6): 3980 - 3988. [Abstract] [Full Text] [PDF]

				X. Shan, A. Bourdeau, A. Rhoton, D. E. Wells, E. H. Cohen, B. E. Landgraf, and R. G. E. Palfree Characterization and Mapping to Human Chromosome 8q24.3 of Ly-6-Related Gene 9804 Encoding an Apparent Homologue of Mouse TSA-1 J. Immunol., January 1, 1998; 160(1): 197 - 208. [Abstract] [Full Text] [PDF]

				T. Mori, K. Ando, K. Tanaka, Y. Ikeda, and Y. Koga Fas-Mediated Apoptosis of the Hematopoietic Progenitor Cells in Mice Infected With Murine Cytomegalovirus Blood, May 15, 1997; 89(10): 3565 - 3573. [Abstract] [Full Text] [PDF]