title: Rapid deletion of antigen-specific CD4+ T cells following infection represents a strategy of immune evasion and persistence for Anaplasma marginale.
abstract: Acquired T cell immunity is central for protection against infection. However, the immunological consequences of exposing memory T cells to high Ag loads during acute and persistent infection with systemic pathogens are poorly understood. We investigated this by using infection with Anaplasma marginale, a ruminant pathogen that replicates to levels of 10(9) bacteria per ml of blood during acute infection and maintains mean bacteremia levels of 10(6) per ml during long-term persistent infection. We established that immunization-induced Ag-specific peripheral blood CD4(+) T cell responses were rapidly and permanently lost following infection. To determine whether these T cells were anergic, sequestered in the spleen, or physically deleted from peripheral blood, CD4(+) T lymphocytes from the peripheral blood specific for the major surface protein (MSP) 1a T cell epitope were enumerated by DRB3*1101 tetramer staining and FACS analysis throughout the course of immunization and challenge. Immunization induced significant epitope-specific T lymphocyte responses that rapidly declined near peak bacteremia to background levels. Concomitantly, the mean frequency of tetramer(+)CD4(+) cells decreased rapidly from 0.025% before challenge to a preimmunization level of 0.0003% of CD4(+) T cells. Low frequencies of tetramer(+)CD4(+) T cells in spleen, liver, and inguinal lymph nodes sampled 9-12 wk postchallenge were consistent with undetectable or unsustainable Ag-specific responses and the lack of T cell sequestration. Thus, infection of cattle with A. marginale leads to the rapid loss of Ag-specific T cells and immunologic memory, which may be a strategy for this pathogen to modulate the immune response and persist.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.
authors.forename: Sushan
authors.initials: S
authors.lastname: Han
authors.forename: Junzo
authors.initials: J
authors.lastname: Norimine
authors.forename: Guy H
authors.initials: GH
authors.lastname: Palmer
authors.forename: Waithaka
authors.initials: W
authors.lastname: Mwangi
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Lahmers
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Brown
mesh_terms: D042322:Anaplasma marginale / Q000276:immunology*; D000712:Anaplasmosis / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000382:microbiology; D017637:Clonal Deletion / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007156:Immunologic Memory; D009928:Organ Specificity / Q000276:immunology; D013997:Time Factors
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018984:Epitopes, T-Lymphocyte; C449089:major surface protein 1a, Anaplasma