Year: 2010
Type: dissertation
Abstract: We have performed an initial screening of the phenotype caused by null-mutation of the gene encoding the C<beta>2 catalytic subunit of PKA in mice. The C<beta>2 subunit is enriched in immune cells such as T-, B- and NK cells. We found that PKA catalytic activity was increased in cells isolated from immune organs such as thymus, spleen and LN. Moreover, we observed anti-CD3/CD28-induced increased proliferation of cells isolated from the spleen and thymus but not LN. Using flow cytometry we demonstrated that the relative number of B cells was reduced in the LN, whereas in the spleen B cells were reduced and NK cells were increased. The relative number of the different T cells subsets was not changed in the thymus whereas in the LN and spleen CD4+ cells were significantly increased compared to wt mice. This was most probably due to a relative increase in Th1 lineage since the relative number of Th2 cells appeared unaltered and Treg cells (CD25+FoxP3+) were significantly reduced in the LN and spleen. By monitoring the relative expression of the homing receptor CD62L and the activation marker CD69 we found that C<beta>2 null-mutation may abrogate the development of T cells from naïve to memory cells, implying that the C<beta>2 mice are devoid or harbor reduced number of memory T cells. \nTaken together, our results demonstrate that C<beta>2 KO results in a complex phenotype associated with the immune system. A reduction in the Treg which are engaged in the maintenance of immunological self-tolerance and suppressive control of excessive immune responses to foreign antigens might imply that C<beta>2 KO animals may develop autoimmune disease and/or might have a different susceptibility to tumor development. Moreover, a block in the development of memory T cells might imply that the C<beta>2 KO mice are more susceptible to infections. To what extent one or both of these suggestions are true for the C<beta>2 KO will need further investigation.
Author: Renata Noemia Alves de Almeida
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Universitetet i Oslo
OpenAlex ID: W2398982053