Gambiense human african trypanosomiasis and immunological memory: effect on phenotypic lymphocyte profiles and humoral immunity.

Abstract

In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and that B-cell dysfunction might not be that severe as in mouse models.

• Authors: Veerle Lejon, Dieudonné Mumba Ngoyi, Luc Kestens, Luc Boel, Barbara Barbé, Victor Kande Betu, Johan van Griensven, Emmanuel Bottieau, Jean-Jacques Muyembe Tamfum, Jan Jacobs, Philippe Büscher
• Journal: PLoS pathogens (PLoS Pathog) Vol. 10 Issue 3 Pg. e1003947 (Mar 2014) ISSN: 1553-7374 [Electronic] United States
• PMID: 24603894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Protozoan

Topics

• Adult
• Antibodies, Protozoan (blood, immunology)
• B-Lymphocytes (immunology)
• Female
• Flow Cytometry
• Humans
• Immunity, Humoral (immunology)
• Immunologic Memory (immunology)
• Male
• Phenotype
• Trypanosoma brucei gambiense (immunology)
• Trypanosomiasis, African (blood, immunology)