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.
authors.affiliation: Infectious Disease Service, Department of Medicine and Immunology Program, Memorial Sloan-Kettering Institute, New York, New York 10021, USA. tumar@mskcc.org
authors.forename: Roman A
authors.initials: RA
authors.lastname: Tuma
authors.forename: Rielle
authors.initials: R
authors.lastname: Giannino
authors.forename: Patrick
authors.initials: P
authors.lastname: Guirnalda
authors.forename: Ingrid
authors.initials: I
authors.lastname: Leiner
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000942:Antigens, Bacterial; D019013:CD40 Antigens; D016056:Immunodominant Epitopes