Delayed Clearance ofEhrlichia chaffeensisInfection in CD4+T-Cell Knockout Mice†

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Abstract
Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsiaEhrlichia chaffeensis. To examine the role of helper T cells in host resistance to this macrophage-tropic bacterium, we assessedE. chaffeensisinfections 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-Abbtm1mice lacking helper T cells developed persistent infections that were not resolved even after several months. CD4+T-cell-deficient, B6.129S6-Cd4tm1Knwmice 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-Cd4tm1Knwmice did not. The B6.129S6-Cd4tm1Knwmice also developed activeE. 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 secondE. chaffeensisinfection. The data reported here suggest that the cell-mediated immunity, orchestrated by CD4+T cells is critical for conferring rapid clearance ofE. chaffeensis.