Selected articles November 2014:
New insights into human peripherally induced regulatory CD8+ T cells
The Suppressive Function of Human CD8+ iTregs is Inhibited by IL-1β and TNFα
U. Bjarnadottir, A. L. Lemarquis, S. Halldorsdottir, J. Freysdottir and B. R. Ludviksson
In a study from an Icelandic research group it is delineated how the innate immune system is capable of directly influence both the de novo development and function of human peripherally induced regulatory CD8+ T cells (CD8+ iTregs).
– In particular we demonstrate that the initial pro-inflammatory response has a negative tolerogenic effect mediated through reduced IL-10 and TGF-beta1 driven mechanism, says Björn Ludviksson, principal investigator.
The study provides direct evidence for the role of IL-2 and TGF-beta in human CD8+ iTreg differentiation and that their suppressive function is inhibited in the presence of IL-1beta and TNFalpha, which may be linked to their effect to reduce IL-10 and TGF-beta1 secretion.
– One of the greatest joy of all scientific work is to participate in a collaborative effort involving lot of hard working people dedicated to tackle difficult basic biological questions. The most fun regarding this work in particular was to discover how significant proportion of the CD8+ human T-cells can be induced into development of iTregs and the major regulatory role of the innate immune system upon that pathway, Björn Ludviksson conlcudes.
CD3G – a candidate gene for autoimmunity?
CD3G Gene Defects in Familial Autoimmune Thyroiditis
B. Gokturk, S. Keles, M. Kirac, H. Artac, H. Tokgoz, S. N. Guner, U. Caliskan, Z. Caliskaner, M. van der Burg, J. van Dongen, N. V. Morgan and I. Reisli
CD3G, the gene for the CD3gamma chain, part of the T-cell co-receptor, should be studied as a candidate gene for autoimmunity, suggests a group from Konya Training and Research Hospital in Turkey. In a study in the November issue of Scandinavian Journal of Immunology the group reports frequent and multiple autoimmune findings in patients with CD3gamma deficiency. In the study, three new CD3gamma-deficient siblings from a consanguineous family is reported. Further a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation was re-evaluated. All five patients displayed several different autoimmune symptoms, but also family members that are heterozygous carriers of mutations display autoimmunity.
Bahar Göktürk who directed the research in this study, says that CD3G could be a candidate gene for autoimmunity.
– I think CD3 gamma deficiency is more than we expected especially in countries that have high frequencies of consanguinity. I hope that this study can create an awareness about the association between autoimmune diseases and immune deficiency.
CD3gamma-deficiency is a very rare condition, up to date only nine patients have been described, including the ones in this study. In addition it seems like siblings with the same mutation may have different clinical courses, which may be due to existence of undefined modifying genes in these individuals. Interestingly, CD3gamma-deficient patients have normal immunoglobulin levels and antibody responses, and not even T cell counts or functions might be affected. In the present study, only one of the patients had markedly abnormal T cell functions.
In conclusion, the authors suggest that CD3gamma-deficiency should be kept in mind when investigating patients with autoimmunity and atopic diseases