Vielkind, Susina; (2003) The Role of the GTPase Rho in T cell Adhesion and Migration. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The guanine nucleotide binding protein Rho has essential functions in the development of T lymphocytes in the thymus. Rho is thus important for the survival of pre-T cells. Activation of RhoA also regulates the efficiency of thymocyte selection: positive selection is more efficient in thymocytes expressing active RhoA and less efficient in thymocytes that have lost Rho function. To explore the mechanisms used by RhoA to control thymocyte biology the role of RhoA in the regulation of integrin- rnediated cell adhesion and migration was examined. The cells used for these experiments were primary T cells from transgenic mice expressing either an active allele of RhoA in the T cell compartment or T cells expressing Clostridium botulinum C3 transferase which selectively ribosylates Rho and prevents its function. In primary T cells it was seen that RhoA activation is sufficient to stimulate β1 and β2 integrin-mediated adhesion. Integrin function is important for two aspects of T cell biology: the interaction of T cells with antigen-presenting cells (APC) and the ability of cells to migrate. In the present study the role of RhoA in these two processes was compared. It was seen that the level of RhoA activity was critical for thymocyte migration to chemokines. In contrast, activation of RhoA did not potentiate the ability of T cells to form antigen specific conjugates with APCs nor was Rho function absolutely required for this process. The regulatory actions of RhoA on integrins thus have a selective role on T cells, they do not facilitate and stabilize contacts between the T cell and cells presenting antigen/MHC complexes (APCs), rather they are important for lymphocyte motility.

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