title: Bim mediates the elimination of functionally unfit Th1 responders from the memory pool.
abstract: Selective clonal deletion in the CD4(+) T cell compartment during the transition from effector to memory is accompanied by enhanced expression of the pro-apoptotic Bcl-2 family member Bim. Here, we show that Bim deficiency enables the survival of poorly functional Th1 responders that are normally eliminated during contraction. However, rescued bim(-/-) CD4(+) "memory" T cells continued to demonstrate deficient effector functions, poor sensitivity to antigen and an inability to respond to secondary challenge. Our results demonstrate that Bim activity plays a key role in shaping the CD4(+) memory T cell repertoire, ensuring the emergence of highly functional CD4(+) memory T cells and the elimination of Th1 effector cells with sub-optimal function. We propose that Bim is a key mediator of T cell death in the absence of appropriate TCR-driven activation and differentiation.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Jay
authors.forename: Diana M
authors.initials: DM
authors.lastname: Mitchell
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Williams
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D015870:Gene Expression; D007156:Immunologic Memory; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins