Loss of either CD4+ or CD8+ T cells does not affect the magnitude of protective immunity to an intracellular pathogen, Francisella tularensis strain LVS.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Loss of either CD4+ or CD8+ T cells does not affect the magnitude of protective immunity to an intracellular pathogen, Francisella tularensis strain LVS.

J Immunol. 1996 Dec 1;157(11):5042-8. Unique Identifier : AIDSLINE MED/97098736
Yee D; Rhinehart-Jones TR; Elkins KL; Laboratory of Enteric and Sexually Transmitted Diseases, Division; of Bacterial Products, Center for Biologics Evaluation and; Research, Rockville, MD 20852, USA.

Abstract: 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.

Keywords: beta 2-Microglobulin/DEFICIENCY/GENETICS Animal Antigens, CD4/GENETICS/METABOLISM CD4-Positive T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Francisella tularensis/*IMMUNOLOGY/PATHOGENICITY Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Nude Receptors, Antigen, T-Cell, alpha-beta/GENETICS/METABOLISM Receptors, Antigen, T-Cell, gamma-delta/GENETICS/METABOLISM T-Lymphocyte Subsets/IMMUNOLOGY Tularemia/ETIOLOGY/*IMMUNOLOGY JOURNAL ARTICLE
970228
M9721852

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