title: Delayed clearance of Ehrlichia chaffeensis infection in CD4+ T-cell knockout mice.
abstract: Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. To examine the role of helper T cells in host resistance to this macrophage-tropic bacterium, we assessed E. chaffeensis infections in three mouse strains with differing functional levels of helper T cells. Wild-type, C57BL/6J mice resolved infections in approximately 2 weeks. Major histocompatibility complex class II (MHCII) knockout, B6.129-Abb(tm1) mice lacking helper T cells developed persistent infections that were not resolved even after several months. CD4+ T-cell-deficient, B6.129S6-Cd4(tm1Knw) mice cleared the infection, but the clearance took 2 weeks longer than it did for wild-type mice. C57BL/6J mice resolved infection more rapidly following a second experimental challenge, but B6.129S6-Cd4(tm1Knw) mice did not. The B6.129S6-Cd4(tm1Knw) mice also developed active E. chaffeensis-specific immunoglobulin G responses that were slightly lower in concentration and slower to develop than that observed in C57BL/6J mice. E. chaffeensis-specific cytotoxic T cells were not detected following a single bacterial challenge in any mouse strain, including wild-type C57BL/6J mice. However, the cytotoxic T-cell activity developed in all three mouse strains, including the MHCII and CD4+ T-cell knockouts, when challenged with a second E. chaffeensis infection. The data reported here suggest that the cell-mediated immunity, orchestrated by CD4+ T cells is critical for conferring rapid clearance of E. chaffeensis.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA. rganta@vet.k-state.edu
authors.forename: Roman R
authors.initials: RR
authors.lastname: Ganta
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Cheng
authors.forename: Melinda J
authors.initials: MJ
authors.lastname: Wilkerson
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Chapes
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015704:CD4 Antigens / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018469:Ehrlichia chaffeensis / Q000276:immunology* / Q000302:isolation & purification*; D016873:Ehrlichiosis / Q000276:immunology* / Q000382:microbiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000907:Antibodies, Bacterial; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G