T cells and cytokines in mice susceptible and resistant to candida albicans infection

Wanasaengsakul, Siripen (2004). T cells and cytokines in mice susceptible and resistant to candida albicans infection PhD Thesis, School of Dentistry, The University of Queensland.

       
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Author Wanasaengsakul, Siripen
Thesis Title T cells and cytokines in mice susceptible and resistant to candida albicans infection
Formatted title
T cells and cytokines in mice susceptible and resistant to candida albicans infection
School, Centre or Institute School of Dentistry
Institution The University of Queensland
Publication date 2004-12
Thesis type PhD Thesis
Supervisor Associate Professor Robert B, Ashman
Associate Professor Neil W, Savage
Total pages 198
Collection year 2004
Language eng
Subjects L
320899 Dentistry not elsewhere classified
730112 Oro-dental and disorders
Formatted abstract
The general objective of this work was to investigate the role of T cells, and specifically CD4+ lymphocytes, in host responses against systemic and oropharyngeal C. albicans infection in CBA/CaH and BALB/c mice.

The Candida-specific proliferative response of CD4+ and CD8+ lymphocytes from spleen and lymph nodes of both mouse strains was evaluated in vitro. The response of splenic CD4+ lymphocytes from both naive and immunized CBA/CaH mice was stronger than that of BALB/c mice, whereas the proliferative response of unfractionated spleen cells from immune CBA/CaH mice was less than that of BALB/c mice. When compared with CD4+ cells alone, mixed CD4+ and CD8+ cells from immunized CBA/CaH mice showed a poorer response than cells from BALB/c mice, suggesting that the reduced response of unfractionated cells from this strain resulted from an interaction between CD4+ and CD8+ cells. In contrast, lymphoproliferation by either unfractionated or purified CD4+ cells from lymph nodes was unchanged after oral immunization, and was equivalent between CBA/CaH and BALB/c mice.

Expression of cell surface activation markers and cytokine production by spleen cells was determined during the course of systemic infection. There was no significant difference m the proportion of any surface marker (CD25, CD44, CD45RB, or CD62L) expressed on splenic CD4+ lymphocytes in either CBA/CaH or BALB/c mice. However, the proportion of CD44+ cells tended to be greater in BALB/c mice during the course of oropharyngeal candidiasis. Both Candida-specific Thl (IFN-γ) and Th2 (IL-4, IL-10) cytokines were produced by splenic CD4+ cells from CBA/CaH and BALB/c mice during the course of systemic infection; however, only IL-10 was synthesized by lymph node CD4+ cells from orally infected mice. Thus, the increased tissue susceptibility to C. albicans of CBA/CaH mice appeared to correlate with the early production of IL-10 by CD4+ cells.

The function of activated Candida-specific T cells was further evaluated using Candida antigen-specific T cell lines. There were no significant differences between lines derived from CBA/CaH and BALB/c mice in the expression of any surface markers, T cell lines generated from splenic CD4+ lymphocytes of naŃ—ve CBA/CaH mice produced both Thl and Th2 cytokines, with a relatively high amount of IL-10, whereas those from naïve BALB/c mice produced only Thl cytokines, A shift to IL-10 production was demonstrated in T cell lines generated from systemically immunized BALB/c mice. The cytokine profiles of lines derived from lymph node cells differed from those derived from spleen cells, in that only IL-10 was detected in CBA/CaH T cell lines, whereas both IFN-γ and IL-10 were produced in lines from naive BALB/c mice.

The low proliferative response of lymph node cells after oral infection suggested a significant role for innate immunity in the host response. This postulate was substantiated by the demonstration that nude mice were able to clear a low grade oral infection, a finding that led to an investigation of effector precursor cell production in bone marrow, Candida antigen suppressed in vitro colony formation by bone marrow from naïve CBA/CaH, but not BALB/c mice, but this effect was not demonstrable during the course of systemic or oral infection in vivo. However, in nude CBA/CaH mice, persistent oral infection reduced the number of bone marrow precursor cells, whereas it did not suppress the precursor cell production in nude BALB/c mice. The presence of T cells in wild type and reconstituted nude BALB/c, but not CBA/CaH mice, was associated with increased colony formation in acute infection.

In conclusion, the role of T cells in the responses against systemic C. albicans infection was different from that in oral infection in both CBA/CaH and BALB/c mice. Early IL- 10 production was associated with immunopathology in CBA/CaH mice, but late IL-10 synthesis may be an immunoregulatory stage in BALB/c mice. A suppressive effect of Candida antigen on bone marrow production may be part of mechanisms linked to tissue susceptibility to infection in CBA/CaH mice.
Keyword Candidiasis
Candida albicans
T cells
Cytokines

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
 
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Created: Fri, 24 Aug 2007, 18:25:51 EST