Rapid and long-term disappearance of CD4+ T lymphocyte responses specific for Anaplasma marginale major surface protein-2 (MSP2) in MSP2 vaccinates following challenge with live A. marginale

Jeffrey R Abbott; Guy H Palmer; Kimberly A Kegerreis; Peter F Hetrick; Chris J Howard; Jayne C Hope; Wendy C Brown

doi:10.4049/jimmunol.174.11.6702

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Rapid and long-term disappearance of CD4+ T lymphocyte responses specific for Anaplasma marginale major surface protein-2 (MSP2) in MSP2 vaccinates following challenge with live A. marginale

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Rapid and long-term disappearance of CD4+ T lymphocyte responses specific for Anaplasma marginale major surface protein-2 (MSP2) in MSP2 vaccinates following challenge with live A. marginale

Jeffrey R Abbott, Guy H Palmer, Kimberly A Kegerreis, Peter F Hetrick, Chris J Howard, Jayne C Hope and Wendy C Brown

The Journal of immunology (1950), Vol.174(11), pp.6702-6715

06/01/2005

DOI: https://doi.org/10.4049/jimmunol.174.11.6702

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https://hdl.handle.net/2376/107771

PMID: 15905510

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Abstract

Enzyme-Linked Immunosorbent Assay - methods

Immunodominant Epitopes - immunology

Leukocytes, Mononuclear - metabolism

Cell Proliferation

Coculture Techniques

Antigens, Bacterial - immunology

Molecular Sequence Data

Antigen-Presenting Cells - microbiology

Interferon-gamma - metabolism

T-Lymphocytes, Regulatory - immunology

CD4-Positive T-Lymphocytes - immunology

Anaplasmosis - microbiology

Immunoglobulin G - biosynthesis

Cattle

Leukocytes, Mononuclear - immunology

Vaccines, Attenuated - administration & dosage

Clostridium - immunology

Leukocytes, Mononuclear - microbiology

Amino Acid Sequence

Bacterial Outer Membrane Proteins - immunology

CD4-Positive T-Lymphocytes - microbiology

Rickettsia - immunology

CD4-Positive T-Lymphocytes - cytology

Anaplasmosis - immunology

CD4-Positive T-Lymphocytes - metabolism

Bacterial Outer Membrane Proteins - administration & dosage

Immunization, Secondary - methods

Antigens, Bacterial - administration & dosage

Cell Survival - immunology

Antigen-Presenting Cells - immunology

Immunodominant Epitopes - administration & dosage

Growth Inhibitors - immunology

Vaccines, Attenuated - immunology

Animals

Bacterial Vaccines - administration & dosage

Bacterial Vaccines - immunology

Lymphocyte Count

Anaplasma marginale - immunology

In humans and ruminants infected with Anaplasma, the major surface protein 2 (MSP2) is immunodominant. Numerous CD4(+) T cell epitopes in the hypervariable and conserved regions of MSP2 contribute to this immunodominance. Antigenic variation in MSP2 occurs throughout acute and persistent infection, and sequentially emerging variants are thought to be controlled by variant-specific Ab. This study tested the hypothesis that challenge of cattle with Anaplasma marginale expressing MSP2 variants to which the animals had been immunized, would stimulate variant epitope-specific recall CD4(+) T cell and IgG responses and organism clearance. MSP2-specific T lymphocyte responses, determined by IFN-gamma ELISPOT and proliferation assays, were strong before and for 3 wk postchallenge. Surprisingly, these responses became undetectable by the peak of rickettsemia, composed predominantly of organisms expressing the same MSP2 variants used for immunization. Immune responsiveness remained insignificant during subsequent persistent A. marginale infection up to 1 year. The suppressed response was specific for A. marginale, as responses to Clostridium vaccine Ag were consistently observed. CD4(+)CD25(+) T cells and cytokines IL-10 and TGF-beta1 did not increase after challenge. Furthermore, a suppressive effect of nonresponding cells was not observed. Lymphocyte proliferation and viability were lost in vitro in the presence of physiologically relevant numbers of A. marginale organisms. These results suggest that loss of memory T cell responses following A. marginale infection is due to a mechanism other than induction of T regulatory cells, such as peripheral deletion of MSP2-specific T cells.

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Title: Rapid and long-term disappearance of CD4+ T lymphocyte responses specific for Anaplasma marginale major surface protein-2 (MSP2) in MSP2 vaccinates following challenge with live A. marginale
Creators: Jeffrey R Abbott - Program in Vector-Borne Disease, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, 99164, USA
Guy H Palmer
Kimberly A Kegerreis
Peter F Hetrick
Chris J Howard
Jayne C Hope
Wendy C Brown
Publication Details: The Journal of immunology (1950), Vol.174(11), pp.6702-6715
Academic Unit: Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
Publisher: United States
Grant note: AI44005 / NIAID NIH HHS AI49276 / NIAID NIH HHS
Identifiers: 99900547355601842
Language: English
Resource Type: Journal article