CD44 is a transmembrane cell surface glycoprotein which has been implicated in various cell processes such as cell adhesion, lymphocyte migration and lymphocyte activation. However, although an important function for CD44 has been suggested by antibody-blocking studies, CD44+/+ mice paradoxically show few defects in immune function. Since compensatory mechanisms, operable in the complete absence of CD44 expression, could account for these apparently contradictory findings, we compared the development and function of CD44+/+ and CD44+/+ lymphocytes when these cells were in direct competition. Radiation bone marrow chimeras made with different combinations of CD44+/+ and CD44"7" donor and recipient mice were employed. CD44"/' progenitor cells were able to fully reconstitute both T and B cell pools when injected into irradiated CD44+/+ or CD44'A recipients. However, chimeras reconstituted with a mixture of CD44"/" and CD44+/+ progenitors showed a deficiency in the generation of CD44"A T cells. This deficit appeared to be due to both reduced thymic homing and impaired intrathymic maturation of CD44+/+ precursors. In contrast, a slight increase in the production of B cells derived from the CD44+/+ progenitors was observed in mixed chimeras, which was independent of precursor trapping in the thymus, as shown in experiments in thymectomised mice. The function of mature CD44+/+ lymphocytes was investigated by assessing immune responses after immunisation or infection of mixed chimeras. As measured by tetramer and intracellular cytokine staining, CD44+/+ CD8+ T cells were shown to respond less well than CD44+/+ cells, while CD44+/+ B cells exhibited a subtle defect in antibody production. Overall, the results demonstrate that CD44 plays a role during lymphocyte development and in the function of mature lymphocytes, which is only apparent when CD44 positive and negative cells are in direct competition.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:634552 |
| Date | January 2005 |
| Creators | Graham, V. A. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1444418/ |
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