Loss of either CD4+ or CD8+ T cells does not affect the magnitude of protective immunity to an intracellular pathogen, Francisella tularensis strain LVS.
Normal mice readily survive a sublethal intradermal (i.d.) infection with Francisella tularensis live vaccine strain (LVS), a model intracellular bacterium, and are strongly protected against subsequent lethal challenge. However, athymic nu/nu mice, which lack mature alphabeta TCR+ T lymphocytes, succumb to i.d. infection within 30 days. Here we characterize the alphabeta T cell subpopulations necessary for both resolution of i.d. infection and generation of optimal protective immunity to LVS. BALB/cByJ mice treated with anti-CD4 or anti-CD8 Abs before i.d. infection survived and cleared bacteria, and anti-CD4- or anti-CD8-treated immune mice survived a very strong i.p. challenge of 10,000 LD50s. Among mutant mice with targeted gene disruptions (knockouts), CD4-, beta2-microglobulin-deficient (which are also CD8-), and gammadelta TCR- mice all resolved a large sublethal i.d. infection. All CD4- and beta2-microglobulin-deficient mice readily survived subsequent lethal i.p. challenge of 10,000 LD50s, even in the absence of specific IgG Abs, as did most (86%) gammadelta TCR- mice. In contrast, alphabeta TCR- mice or alphabeta + gammadelta TCR- mice died about 35 days after i.d. infection. Depletion of gammadelta+ T cells from alphabeta TCR- mice had no effect on mean time to death from i.d. LVS infection. Therefore alphabeta TCR+ cells are required for protection, but either CD4+ or CD8+ T cells are individually sufficient to resolve a large sublethal i.d. LVS infection and to protect against a maximal secondary lethal challenge. These results emphasize the remarkable plasticity of the alphabeta T cell response in protective immunity to intracellular bacteria.
Yee
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Laboratory of Enteric and Sexually Transmitted Diseases, Division of Bacterial Products, Center for Biologics Evaluation and Research, Rockville, MD 20852, USA.
Rhinehart-Jones
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Elkins
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D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005604:Francisella tularensis / Q000276:immunology* / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014406:Tularemia / Q000209:etiology / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D001613:beta 2-Microglobulin