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      Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function

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          Abstract

          Natural killer (NK) and NK T cells are tissue lymphocytes that secrete cytokines rapidly upon stimulation. Here, we show that these cells maintain distinct patterns of constitutive cytokine mRNAs. Unlike conventional T cells, NK T cells activate interleukin (IL)-4 and interferon (IFN)-γ transcription during thymic development and populate the periphery with both cytokine loci previously modified by histone acetylation. Similarly, NK cells transcribe and modify the IFN-γ gene, but not IL-4, during developmental maturation in the bone marrow. Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes.

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          Most cited references23

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          Molecular and functional profiling of memory CD8 T cell differentiation.

          How and when memory T cells form during an immune response are long-standing questions. To better understand memory CD8 T cell development, a time course of gene expression and functional changes in antigen-specific T cells during viral infection was evaluated. The expression of many genes continued to change after viral clearance in accordance with changes in CD8 T cell functional properties. Even though memory cell precursors were present at the peak of the immune response, these cells did not display hallmark functional traits of memory T cells. However, these cells gradually acquired the memory cell qualities of self-renewal and rapid recall to antigen suggesting the model that antigen-specific CD8 T cells progressively differentiate into memory cells following viral infection.
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            Mouse CD1-specific NK1 T cells: development, specificity, and function.

            NK1 T cells are a specialized population of alpha/beta T cells that coexpress receptors of the NK lineage and have the unique potential to very rapidly secrete large amounts of cytokines, providing early help for effector cells and regulating the Th1 or Th2 differentiation of some immune responses. NK1 T cells express a restricted TCR repertoire made of an invariant TCR alpha chain, V alpha 14-J alpha 281, associated with polyclonal V beta 8, V beta 7, and V beta 2 TCR beta chains. NK1 T cells recognize the products of the conserved family of MHC class I-like CD1 genes, apparently in the absence of foreign antigens. Thus, this novel regulatory pathway, which straddles the innate and the adaptive immune systems, is unique in that its activation may not require associative recognition of antigen. Here, we review the specificity and function of mouse NK1 T cells, and we discuss the relationship of this lineage to mainstream T cells and NK cells.
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              Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene.

              The c-abl proto-oncogene, which encodes a cytoplasmic protein-tyrosine kinase, is expressed throughout murine gestation and ubiquitously in adult mouse tissues. However, its levels are highest in thymus, spleen, and testes. To examine the in vivo role of c-abl, the gene was disrupted in embryonic stem cells, and the resulting genetically modified cells were used to establish a mouse strain carrying the mutation. Most mice homozygous for the c-abl mutation became runted and died 1 to 2 weeks after birth. In addition, many showed thymic and splenic atrophy and a T and B cell lymphopenia.
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                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                6 October 2003
                : 198
                : 7
                : 1069-1076
                Affiliations
                [1 ]Howard Hughes Medical Institute, Departments of Medicine and Microbiology/Immunology, University of California San Francisco, San Francisco, CA 94143
                [2 ]The La Jolla Institute of Allergy and Immunology, San Diego, CA 92121
                Author notes

                Address correspondence to Richard M. Locksley, University of California San Francisco, Box 0654, C-443, 521 Parnassus Avenue, San Francisco, CA 94143. Phone: (415) 476-5859; Fax: (415) 476-9364; email: locksley@ 123456medicine.ucsf.edu

                Article
                20030630
                10.1084/jem.20030630
                2194220
                14530376
                31ea19da-28b9-4e86-a08a-3ab98f4084a3
                Copyright © 2003, The Rockefeller University Press
                History
                : 17 April 2003
                : 26 June 2003
                : 11 August 2003
                Categories
                Article

                Medicine
                nk cells,cytokine mrnas,ifn-γ,il-4,nk t cells
                Medicine
                nk cells, cytokine mrnas, ifn-γ, il-4, nk t cells

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