TY  - JOUR
A1  - Giampaolo, Sabrina
A1  - Wójcik, Gabriela
A1  - Serfling, Edgar
A1  - Patra, Amiya K.
T1  - Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells
JF  - Oncotarget
N2  - The role of IL-2 in HSC maintenance is unknown. Here we show that Il2\(^{−/-}\) mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2\(^{−/-}\) mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2\(^{−/-}\) mice shows that the IL-2-T\(_{reg}\) cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of T\(_{reg}\) activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring T\(_{reg}\) population successfully rescued HSC maintenance in Il2\(^{-/-}\) mice, preventing IFN-γ activity could do the same even in the absence of T\(_{reg}\) cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis.
KW  - immunity
KW  - hematopoietic stem cells
KW  - IL-2
KW  - treg cells
KW  - IL-10
KW  - IFN-γ
KW  - immunology and microbiology section
KW  - immune response
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170947
VL  - 8
IS  - 18
ER  - 
TY  - JOUR
A1  - Karulin, Alexey Y.
A1  - Karacsony, Kinga
A1  - Zhang, Wenji
A1  - Targoni, Oleg S.
A1  - Moldova, Ioana
A1  - Dittrich, Marcus
A1  - Sundararaman, Srividya
A1  - Lehmann, Paul V.
T1  - ELISPOTs produced by CD8 and CD4 cells follow Log Normal size distribution permitting objective counting
JF  - Cells
N2  - Each positive well in ELISPOT assays contains spots of variable sizes that can range from tens of micrometers up to a millimeter in diameter. Therefore, when it comes to counting these spots the decision on setting the lower and the upper spot size thresholds to discriminate between non-specific background noise, spots produced by individual T cells, and spots formed by T cell clusters is critical. If the spot sizes follow a known statistical distribution, precise predictions on minimal and maximal spot sizes, belonging to a given T cell population, can be made. We studied the size distributional properties of IFN-γ, IL-2, IL-4, IL-5 and IL-17 spots elicited in ELISPOT assays with PBMC from 172 healthy donors, upon stimulation with 32 individual viral peptides representing defined HLA Class I-restricted epitopes for CD8 cells, and with protein antigens of CMV and EBV activating CD4 cells. A total of 334 CD8 and 80 CD4 positive T cell responses were analyzed. In 99.7% of the test cases, spot size distributions followed Log Normal function. These data formally demonstrate that it is possible to establish objective, statistically validated parameters for counting T cell ELISPOTs.
KW  - ELISPOT
KW  - software
KW  - IFN-γ
KW  - IL-17
KW  - T cells
KW  - Normal Distribution
KW  - spot size
KW  - gating
KW  - cytokines
KW  - IL-2
KW  - IL-4
KW  - IL-5
KW  - CD8
KW  - CD4
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149648
VL  - 4
IS  - 1
ER  -