Journal article
Rapid deletion of antigen-specific CD4+ T cells following infection represents a strategy of immune evasion and persistence for Anaplasma marginale
The Journal of immunology (1950), Vol.181(11), pp.7759-7769
12/01/2008
Handle:
https://hdl.handle.net/2376/113677
PMID: 19017965
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.
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Details
- Title
- Rapid deletion of antigen-specific CD4+ T cells following infection represents a strategy of immune evasion and persistence for Anaplasma marginale
- Creators
- Sushan Han - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USAJunzo NorimineGuy H PalmerWaithaka MwangiKevin K LahmersWendy C Brown
- Publication Details
- The Journal of immunology (1950), Vol.181(11), pp.7759-7769
- Academic Unit
- Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
- Publisher
- United States
- Grant note
- T32 AI007025 / NIAID NIH HHS R01 AI044005-06 / NIAID NIH HHS R01-AI44005 / NIAID NIH HHS R01 AI044005 / NIAID NIH HHS R01 AI053692 / NIAID NIH HHS R01-AI053692 / NIAID NIH HHS R01 AI053692-01A1 / NIAID NIH HHS
- Identifiers
- 99900548292301842
- Language
- English
- Resource Type
- Journal article