Chlamydia trachomatis is well-established as a major cause of sexually transmitted disease in the United States despite the availability of effective antibiotics. Infection in women commonly remains unnoticed but may then ascend the genital tract producing salpingitis and potentially tubal obstruction. While a strong immune response develops in humans to chlamydial genital infection, immunity to reinfection is apparently short- lived. The mechanism of this immunity and the reason for its short length are unknown. In animal models, both antibody and cell-mediated immunity (CMI) have been found to play important roles. CMI appears to be of major importance in the mouse, since B cell-deficient mice infected with the agent of mouse pneumonitis (MoPn) a C. trachomatis biovar, are able to resolve the infection in the same time frame as controls. This study will examine the role of different T cell subpopulations to determine their function in resolution of and resistance to chlamydial genital infection. Populations of spleen cells enriched for T cells bearing the L3T4 (helper/inducer) or Lyt 2 (cytotoxic/suppressor) surface markers will be injected into nude mice and their effect on the course of MoPn genital infection determined. Nude mice are normally unable to resolve a chlamydial infection and remain chronically infected. The antibody and CMI response of the recipient mice will be evaluated. Splenic T cell will be cultured with MoPn antigen, antigen processing cells, and interleukin 2 to select an antigen-specific T cell population. This population will be characterized and used to reconstitute nude mice. Furthermore, specific chlamydial outer membrane components including the major outer membrane protein, a 66 Kd protein, and lipopolysaccharide will be used to induce antigen-specific T cell clones. By use of this methodology, an insight may be gained into which chlamydial components bear epitopes responsible for eliciting a protective T cell response. Specific T helper cells will be generated which will stimulate only an IgA response to MoPn antigens in order to determine whether secretory antibody can contribute to immunity in the mouse. Finally, the role of gamma interferon will be investigated by the passive transfer of recombinant murine gamma interferon to infected nude mice and by the production of T cell clones secreting gamma interferon.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026328-03
Application #
3140097
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1988-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1992-03-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Jiang, Janina; Champion, Cheryl I; Wei, Bo et al. (2013) CD8?CXCR5? T cells regulate pathology in the genital tract. Infect Dis Obstet Gynecol 2013:813238
Jiang, Janina; Kelly, Kathleen A (2012) Isolation of lymphocytes from mouse genital tract mucosa. J Vis Exp :e4391
Kar, Upendra K; Jiang, Janina; Champion, Cheryl I et al. (2012) Vault nanocapsules as adjuvants favor cell-mediated over antibody-mediated immune responses following immunization of mice. PLoS One 7:e38553
Jiang, Janina; Kelly, Kathleen A (2011) Phenotype and function of regulatory T cells in the genital tract. Curr Trends Immunol 12:89-94
Moniz, Raymond J; Chan, Ann M; Gordon, Lynn K et al. (2010) Plasmacytoid dendritic cells modulate nonprotective T-cell responses to genital infection by Chlamydia muridarum. FEMS Immunol Med Microbiol 58:397-404
Kelly, Kathleen A; Chan, Ann M; Butch, Anthony et al. (2009) Two different homing pathways involving integrin ?7 and E-selectin significantly influence trafficking of CD4 cells to the genital tract following Chlamydia muridarum infection. Am J Reprod Immunol 61:438-45
Shimazaki, Kaori; Chan, Ann M; Moniz, Raymond J et al. (2009) Blockade of epithelial membrane protein 2 (EMP2) abrogates infection of Chlamydia muridarum murine genital infection model. FEMS Immunol Med Microbiol 55:240-9
Champion, Cheryl I; Kickhoefer, Valerie A; Liu, Guangchao et al. (2009) A vault nanoparticle vaccine induces protective mucosal immunity. PLoS One 4:e5409
Kickhoefer, Valerie A; Han, Muri; Raval-Fernandes, Sujna et al. (2009) Targeting vault nanoparticles to specific cell surface receptors. ACS Nano 3:27-36
King, M; Poya, H; Rao, J et al. (2009) CXCL13 expression in Chlamydia trachomatis infection of the female reproductive tract. Drugs Today (Barc) 45 Suppl B:125-34

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