Complement receptor 2 (CR2/CD21) in experimental African trypanosomiasis
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Date
2009
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Publisher
ORCID
Type
Degree Level
Masters
Abstract
African trypanosomes are protozoan blood parasites that infect both humans and livestock. BALB/c mice are highly susceptible to experimental infections by Trypanosoma congolense while C57BL/6 mice are relatively resistant, as measured by degree and pattern of parasitemia and survival time. Rapid death observed in highly susceptible BALB/c mice is due to a systemic inflammatory response syndrome (SIRS). A small subset of pathogenic, MHC class II-restricted CD4+ T cells, activated during the course of T. congolense infections, mediates early mortality in infected highly susceptible BALB/c mice via excessive synthesis of the cytokine IFN-gamma. Since these pathogenic T cells are matrix–adherent, they could be distinguished from conventional Th1 cells. There is a possibility that this subpopulation of T cells has unique surface markers.
The complement system is highly activated in African trypanosomiasis, leading to persistent hypocomplementemia. Amplification of the alternative pathway of complement is faster in BALB/c mice than in C57BL/6 mice and the degradation of complement component C3b to complement component C3d, during the amplification of the alternative pathway of complement, proceeds faster in BALB/c than in C57BL/6 mice (Ogunremi et al., 1993). T. congolense-infected BALB/c mice have more immune complexes containing trypanosomal variant surface glycoprotein (VSG) than C57BL/6 mice in their plasma (Pan & Tabel, unpublished). T. congolense-infected BALB/c mice might have more VSG-C3d immune complexes than infected C57BL/6 mice. The receptor for complement component C3d is the cell surface molecule CR2, also referred to as CD21. It is known that CR2 is widely expressed on B lymphocytes and follicular dendritic cells. There is also some evidence that CR2 is expressed on a subpopulation of activated T cells. Binding of VSG-C3d immune complexes to the complement receptor CR2 might costimulate the CR2+ T cells to produce IFN-ã. I hypothesize that IFN-ã-producing T cells in T. congolense-infected BALB/c mice are CR2+ and that the CR2+ T cells increase in numbers in experimental murine T. congolense infections.
Kinetic studies were carried out by staining spleen cells of T. congolense-infected BALB/c mice for the presence of CR2 on T cells (CD3+ cells). Total numbers of spleen cells showed a 5-fold increase with progressive T. congolense infections. The total numbers of T cells in the spleen showed a 7-fold increase at day 8 post infection. The total numbers of CR2+ T cells in the spleen showed a 3 to 7-fold increase with progressive infection. Parallel studies on B lymphocytes (CD19+ cells) showed that absolute numbers of B cells in the spleen had a 5 to 6-fold increase with progressive infection. Absolute numbers of CR2+ B cells in the spleen showed a 4-fold increase at day 7 post infection. The total numbers of CR2+ cells in the spleen showed an increase while the mean numbers of CR2 molecules per cell showed a reduction with progressive infection.
These results show that CR2+ T cells in the spleen increase in numbers with progressive T. congolense infections in BALB/c mice. I suggest that CD4+CR2+ T cells might play a role in the pathogenesis of T. congolense infections.
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Keywords
CR2, Trypanosomiasis, kinetic studies, spleen cells
Citation
Degree
Master of Science (M.Sc.)
Department
Veterinary Microbiology
Program
Veterinary Microbiology