title: Phenotype and function of protective, CD4-independent CD8 T cell memory.
abstract: While the need for CD4 T cells in the generation of CD8 T cell memory has been well documented, the mechanism underlying their requirement remains unknown. Here, we detail an immunization method capable of generating CD8 memory T cells that are indifferent to CD4 T cell help. Using a subunit vaccination that combines polyIC and an agonistic CD40 antibody, we program protective CD4-independent CD8 T cell memory. When cells generated by combined polyIC/CD40 immunization are compared to cells produced following a CD4-dependent vaccination, Listeria monocytogenes, they display dramatic differences, both phenotypically and functionally. The memory cells generated in a CD4-deficient host by polyIC/CD40 immunization provide protection against secondary infectious challenge, whereas cells generated by LM immunization in the same environment do not. Interestingly, combined polyIC/CD40 immunization generates long-term memory cells with low Blimp-1 and elevated Eomes expression despite high expression of Blimp-1 during the primary response. The potency of combined polyIC/CD40 to elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be considered as a vaccine adjuvant in clinical situations where CD4 responses/numbers are compromised.
authors.affiliation: Integrated Department of Immunology, University of Colorado School of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Edwards
authors.forename: Catherine
authors.initials: C
authors.lastname: Haluszczak
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005802:Genes, MHC Class II / Q000235:genetics; D007114:Immunization; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011070:Poly I-C / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D014615:Vaccinia / Q000276:immunology
chemical_list: D000906:Antibodies; D019013:CD40 Antigens; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011070:Poly I-C