|
Paper Reading Endothelial basement membrane laminin a5 selectively inhibits T lymphocyte extravasationinto the brain Chuan Wu & Lydia M Sorokin Nature medicine, 2009 It has been proposed that specificinhibition of T cell lymphocytes into the central nervous system in humanautoimmune disease multiple sclerosis would be a promising way to decrease theinflammation in the CNS. Previous papers have reported that many importantchemokines and molecules participate in the leukocytes penetration into thevessels, such as CCL19, CCL21, CCl2 and integrin a4- and P-selectin. This papertold us that how T lymphocytes traverse the endothelial basement membrane bymeans of EAE model, a CD4+ T lymphocyte-mediated autoimmune disease. They foundthat laminin a4-deficient mice showed reduced EAE disease score and alsosimilar results were obtained by blocking antibodies. The author used in vivoproliferation experiment to exclude the possible defect of proliferativecapacity. Furthermore, their results demonstrated that T lymphocytes migratedinto the CNS through vessel endothelial basement were decreased markedly,however, it did not affect the ratio of leukocytes in the spleen and pLN.  Deletion of CTLA4 on the regulatory T cells during adulthood leads to resistance to autoimmunity. Alison M. Paterson & Arlene H. Sharpe JEM,2015 CTLA4 is a structural homologue of theco-stimulatory receptor CD28, but binds with higher affinity to the sameligands, B7-1(CD80) and B7-2(CD86). Previous data have shown that CTLA4Knockout mice developed systemic autoimmune disease. However, this paperdemonstrated that deletion of CTLA4 in adulthood by means of tamoxifeninduction on ERT2-conditional mice surprisingly lead to EAE resistance.Induction of CTLA4 deletion in adult would promote Tconv and Treg expansion andactivation. Furthermore, arogation of CTLA4 not only in adult T cells or adultTreg cells could enhance Treg suppressive capacity by upregulation ofimmunoinhibitory molecules IL10, PD1 and LAG3. The author put forward theevidence that Treg suppression ability could be independent of CTLA4. |
|
|
