Rescue of CD8 T cell-mediated antimicrobial immunity with a nonspecific inflammatory stimulus Journal Article

Authors: Tuma, R. A.; Giannino, R.; Guirnalda, P.; Leiner, I.; Pamer, E. G.
Article Title: Rescue of CD8 T cell-mediated antimicrobial immunity with a nonspecific inflammatory stimulus
Abstract: Reconstitution of protective immunity by adoptive transfer of pathogen-specific T cells has been successful in patients with compromised cellular immunity. The in vivo effectiveness of in vitro-expanded CD8 CTLs is variable, however. For example, adoptively transferred Listeria monocytogenes-specific CD8 CTLs only confer protective immunity if challenge infection occurs within 48 hours of T cell infusion. Herein we show that transferred CTLs persist in lymphoid compartments for many weeks, but that their response to bacterial challenge decreases during the first week following transfer. While T cells transferred less than 48 hours before infection proliferate, those transferred 7 days before infection die. Remarkably, treatment of mice with anti-CD40 at the time of T cell infusion reprograms transferred T cells, allowing them to proliferate and confer protective immunity upon bacterial challenge 7 days later. Our study demonstrates, for the first time to our knowledge that CD40-mediated stimuli can influence CD8 T cell activation independent of concurrent antigen exposure. The ability to modulate long-term responsiveness of CD8 T cells with a transient, nonspecific inflammatory stimulus has importation implications for adoptive immunotherapy.
Keywords: controlled study; nonhuman; cd8 antigen; lymphocyte proliferation; t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; inflammation; mice, inbred balb c; cellular immunity; immune response; cd4-positive t-lymphocytes; immunodominant epitopes; cytotoxic t lymphocyte; adoptive transfer; adoptive immunotherapy; immunotherapy, adoptive; t lymphocyte activation; immunologic memory; listeria monocytogenes; lymphoid organ; antigens, cd40; microbial immunity; antigens, bacterial; cd40 antigen; humans; priority journal; article
Journal Title: Journal of Clinical Investigation
Volume: 110
Issue: 10
ISSN: 0021-9738
Publisher: American Society for Clinical Investigation  
Date Published: 2002-11-01
Start Page: 1493
End Page: 1501
Language: English
DOI: 10.1172/jci200216356
PUBMED: 12438447
PROVIDER: scopus
PMCID: PMC151819
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Roman Tuma
    5 Tuma
  2. Eric Pamer
    249 Pamer
  3. Ingrid Leiner
    45 Leiner