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 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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