Deficiency of Antigen-Specific B Cells Results in Decreased <i>Trypanosoma cruzi</i> Systemic but Not Mucosal Immunity Due to CD8 T Cell Exhaustion

Sullivan, Nicole; Eickhoff, Christopher S.; Sagartz, John E.; Hoft, Daniel F.

doi:10.4049/jimmunol.1303163

Cited by 34 publications

(43 citation statements)

References 41 publications

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“…In mice exposed to a highly virulent challenge, PD-1 expression and/or other signs of T cell exhaustion are evident (27, 28). Such high dose and acutely lethal infections are also associated with other immunological anomalies (29).…”

Section: Immune Exhaustion During Chronic T Cruzi Infectionmentioning

confidence: 99%

CD8+ T cells in Trypanosoma cruzi infection

2015

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Trypanosoma cruzi infection and Chagas disease remains among the most neglected of the neglected tropical diseases. Despite this, studies of the immune response to T. cruzi have provided new insights in immunology and guidance for approaches for prevention and treatment of the disease. T. cruzi represents one of the very best systems in which to study CD8+ T cell biology; Mice, dogs, and primates (and many other mammals) are all natural hosts for this parasite, the robust T cell responses generated in these hosts can be readily monitored using the full range of cutting edge techniques, and the parasite can be easily modified to express (or not) a variety of tags, reporters, immune enhances and endogenous or model antigens. The infection in most hosts is characterized by vigorous and largely effective immune responses, including CD8+ T cells capable of controlling T. cruzi at the level of the infected host cells. However this immune control is only partially effective and most hosts maintain a low level infection for life. This review addresses the interplay of highly effective CD8+ T cell responses with elaborate pathogen immune evasion mechanisms, including the generation and simultaneous expression of highly variant CD8+ T cell targets and a host cell invasion mechanisms that largely eludes innate immune detection.

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Section: Immune Exhaustion During Chronic T Cruzi Infectionmentioning

confidence: 99%

CD8+ T cells in Trypanosoma cruzi infection

2015

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“…This Th1-driven immune response is the most protective against T. cruzi infection, as previously demonstrated. 36,41,42 In addition, the critical importance of specific antibody-producing B cells for controlling systemic T. cruzi infection was recently reported by Sullivan et al 43 The robust humoral immune response and intense cellular response observed would explain the decreased parasitemia found in mice treated with the combination of both plasmids. These results become even more important since serum levels of enzymes that are markers of muscle damage in chronic Chagas disease (CK, AST and LDH) achieved significantly lower activity levels with respect to controls.…”

Section: Discussionmentioning

confidence: 81%

Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine againstTrypanosoma cruziinfection

Cerny

Albertí

Bivona

et al. 2015

Human Vaccines & Immunotherapeutics

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“…A second dose of anti-CD20 was administered at 2 wk after i.n. AdHu5Ag85Avaccination for the maintenance of B cell depletion (7,8,37,38). This B cell depletion regimen effectively wiped out B cells in the lymph nodes, peripheral blood, and lung before vaccination (data not shown) as verified by immunostaining for CD19 and B220 surface markers expressed on developing and mature B cells.…”

Section: Respiratory Mucosal Adhu5ag85a Vaccination Induces Ag85a-spementioning

confidence: 99%

Role of B Cells in Mucosal Vaccine–Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis

Khera

Afkhami

Lai

et al. 2015

The Journal of Immunology

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Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine–induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine–induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag-specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag-specific T cell responses in the airway and lung interstitium of genetic B cell–deficient (Jh−/− knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and lung interstitium and protection in B cell–depleted wild-type mice to a similar extent as in B cell–competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh−/− KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine–activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine-primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh−/− KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine–induced protective immunity against M. tuberculosis.

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Deficiency of Antigen-Specific B Cells Results in Decreased Trypanosoma cruzi Systemic but Not Mucosal Immunity Due to CD8 T Cell Exhaustion

Cited by 34 publications

References 41 publications

CD8+ T cells in Trypanosoma cruzi infection

CD8+ T cells in Trypanosoma cruzi infection

Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine againstTrypanosoma cruziinfection

Role of B Cells in Mucosal Vaccine–Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis

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