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 matrixadherent, they could be distinguished from conventional Th1 cells. There is a possibility that this subpopulation of T cells has unique surface markers.<p>
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complexes containing trypanosomal variant surface glycoprotein (VSG) than C57BL/6 mice in their plasma (Pan & Tabel, unpublished).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.<p>
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.<p>
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.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-04232009-123902 |
| Date | 27 April 2009 |
| Creators | Munasinghe, Lilani Indika |
| Contributors | Havele, Calliopi, Gordon, John R., Bretscher, Peter A., Misra, Vikram, Tabel, Henry |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-04232009-123902/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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