This proposal describes a lineage marking strategy that is designed to discriminate antigen-experienced T cells from their naive precursors. The key feature of the strategy is the synchronization of a stable genomic alteration with the activation of T cells during immune responses. We will accomplish this synchronization by using the transcriptional control elements of the mouse OX40 locus to drive expression of the Cre recombinase gene. OX40 is a gene that is only expressed in activated T cells, thus Cre expression should be confined to this population of cells. The target for the Cre recombinase will be a novel reporter cassette containing two cistrons. The promoter-proximal cistron will be expressed constitutively in naive T cells and will therefore serve as a marker for these cells. The cistron for this upstream reporter will be flanked by LoxP sites (recognition sites for the Cre recombinase) and will encode a protein that can be readily detectable by flow cytometry or other facile procedures. Cre-mediated recombination during T cell activation will then delete this cistron thereby allowing for expression of a downstream cistron encoding a different reporter molecule. This second reporter will then be used to identify post-activation or antigen-experienced T cells, a population that should include memory T cells. We will use this lineage marking strategy to characterize the immunologic properties of antigen- experienced T cells and to compare then to those of naive precursor cells. Properties such as lifespan, proliferative cycle and sensitivity to activating stimuli will be examined. The development of this marking scheme will expand the repertoire of tools available for the identification of subpopulations of T lymphocytes. Moreover, this study will provide important information about the reactivity and homeostatic activity of antigen-experienced T cells. This approach has general relevance to the issue of how immune responses are regulated and may be of particular value to the study of autoimmune diseases. Such diseases generally depend on chronic autoreactivity of T cells and may arise as a consequence of inadequate immunologic regulation by the antigen- experienced T cells which are the subject of this proposal.

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Briggs, F B S; Ramsay, P P; Madden, E et al. (2010) Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis. Genes Immun 11:199-208
Yazdany, Jinoos; Yelin, Edward (2010) Health-related quality of life and employment among persons with systemic lupus erythematosus. Rheum Dis Clin North Am 36:15-32, vii
Janssens, A Cecile J W; Steyerberg, Ewout W; Jiang, Yebin et al. (2006) Value of the HLA-DRB1 shared epitope for predicting radiographic damage in rheumatoid arthritis depends on the individual patient risk profile. J Rheumatol 33:2383-9
Katz, Patricia P (2006) Childbearing decisions and family size among women with rheumatoid arthritis. Arthritis Rheum 55:217-23
Yelin, Edward H; Trupin, Laura S; Katz, Patricia P (2005) Impact of managed care on the use of biologic agents for rheumatoid arthritis. Arthritis Rheum 53:423-30
Katz, Patricia P (2005) Use of self-management behaviors to cope with rheumatoid arthritis stressors. Arthritis Rheum 53:939-49
von Scheven, E; Elder, M E (2005) Association between beta2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies. Lupus 14:440-4
Yang, Nan; Li, Hongzhe; Criswell, Lindsey A et al. (2005) Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine. Hum Genet 118:382-92
Seldin, Michael F; Morii, Takanobu; Collins-Schramm, Heather E et al. (2004) Putative ancestral origins of chromosomal segments in individual african americans: implications for admixture mapping. Genome Res 14:1076-84
Chang, Wenhan; Shoback, Dolores (2004) Extracellular Ca2+-sensing receptors--an overview. Cell Calcium 35:183-96

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