Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, TH1 lymphocyte clone

J. U. Igietseme, K. H. Ramsey, D. M. Magee, D. M. Williams, T. J. Kincy, R. G. Rank

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148 Scopus citations

Abstract

MoPn-specific T-cell clones were isolated from a T-cell line that was capable of curing chlamydial genital infection by the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) after adoptive transfer. Two clones (designated as 2.14-0 and 2.14-3) were characterized by flow cytometry techniques to be homogenous for L3T4, CD3, and α/β T cell receptor (TcR) T- helper cell markers. The two clones were biovar specific, because they reacted to MoPn but not the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC) or C. trachomatis, serovar type E. Cytokine profile analysis, by a combination of bioassays, ELISA, and slot/Northern blotting for specific cytokine messenger RNAs, further revealed that cultures of antigen-stimulated clone 2.14-0 contained interleukin-2 (IL-2), tumor necrosis factor-alpha, and gamma interferon (a T helper 1 cell [Th1] profile). Clone 2.14-3 was also positive for gamma interferon, a level much lower than that of clone 2.14-0, and negative for IL-4 secretion, suggesting a Th1 profile as well. The ability of these clones to bring about the resolution of the chronic genital chlamydial infection of nude mice was tested by the adoptive transfer of 107 cells of each clone into the mice. By 4 weeks after cell transfer of clone 2.14-0, 81% of recipient nude mice (30 of 37) resolved the disease. In contrast, clone 2.14-3 or a control T-cell clone specific for a heterologous antigen were unable to resolve the infection in 20 recipients in each case, even after 100 days. Interestingly, clone 2.14-0 recipients showed only background titers of specific anti-MoPn serum antibodies (mean titer < 10, range 0-10), suggesting a limited helper function, but recipients of clone 2.14-3 displayed high serum antibody levels of the range of 20-1280, which indicated a significant helper role. The results supported a crucial role for cell-mediated immunity in the resolution of chlamydial genital infection in the mouse: MoPn model system. Also, the results suggested that certain T-cell clonotypes may be more relevant for protection than others in the repertoire of an immune response elicited against a pathogen, a phenomenon that may be related to the epitopes recognized by T cells. Moreover, the availability of characterized, protective, and nonprotective T-cell clones could aid in the direct screening for relevant T-cell epitopes on chlamydial proteins that could be employed for vaccine development.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalRegional Immunology
Volume5
Issue number6
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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