Dianda, Lee; (1996) Immune responses in mice deficient in αβ T cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis examines immune responses in TCR mutant mice which lack αβ T cells. Although αβ T cells are the primary regulators of many aspects of immunity, the extent to which other populations, contribute to particular immune responses has not been fully characterised. The T cell population in TCRα-/- mice consists of γδ T cells and an unusual population of TCRα-β+ cells. The lymphoid tissues in TCRα-/- and TCRβ-/- mice undergo extensive expansion in response to environmental antigens. This does not occur in TCR(β × δ)-/- animals. None of these strains of TCR mutant mice are able to make antibodies to protein antigens. Responses to T independent antigens have been characterised and reveal that in some cases γδ T cells are able to augment the antibody response. Numerous germinal centres were identified in TCRα-/- but not in TCRβ-/- mice in this study. T cells within the germinal centres were usually CD4+ TCRβ+, although CD4+ γδ T cells were also present. Germinal centres were also detected in germfree TCRα-/- mice, although they were less numerous than in TCRα-/- mice kept in specific pathogen free (SPF) conditions. The ability of germinal centre B cells to undergo somatic hypermutation in response to a T independent antigen, phOx-LPS, was investigated. In contrast to the response to haptenated proteins, the Ig repertoire was not dominated by a particular combination of Ig V genes in TCRα-/- nor TCRα+/- mice. In addition, the development of intestinal pathology in TCRα -/- mice was investigated. TCRα-/- mice kept in SPF but not germfree conditions develop inflammatory bowel disease (IBD). Intestinal pathology was not seen in germfree TCRα-/- mice which were colonised with a limited bacterial flora. This suggests that IBD does not occur spontaneously nor does it result form the presence of bacteria, per se, but rather it is initiated by a specific organism or group of organisms which have yet to be identified.

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