TY  - JOUR
A1  - Langenhorst, Daniela
A1  - Haack, Stephanie
A1  - Göb, Selina
A1  - Uri, Anna
A1  - Lühder, Fred
A1  - Vanhove, Bernhard
A1  - Hünig, Thomas
A1  - Beyersdorf, Niklas
T1  - CD28 costimulation of T helper 1 cells enhances cytokine release in vivo
JF  - Frontiers in Immunology
N2  - Compared to naive T cells, differentiated T cells are thought to be less dependent on CD28 costimulation for full activation. To revisit the role of CD28 costimulation in mouse T cell recall responses, we adoptively transferred in vitro generated OT-II T helper (Th) 1 cells into C57BL/6 mice (Thy1.2\(^{+}\)) and then either blocked CD28–ligand interactions with Fab fragments of the anti-CD28 monoclonal antibody (mAb) E18 or deleted CD28 expression using inducible CD28 knock-out OT-II mice as T cell donors. After injection of ovalbumin protein in adjuvant into the recipient mice we observed that systemic interferon (IFN)γ release strongly depended on CD28 costimulation of the Th1 cells, while secondary clonal expansion was not reduced in the absence of CD28 costimulation. For human memory CD4\(^{+}\) T cell responses we also noted that cytokine release was reduced upon inhibition of CD28 costimulation. Together, our data highlight the so far underestimated role of CD28 costimulation for the reactivation of fully differentiated CD4\(^{+}\) T cells.
KW  - CD4\(^{+}\) T helper cells
KW  - T helper 1 cells
KW  - antigenic recall
KW  - CD28 costimulation
KW  - cytokine secretion
KW  - mouse
KW  - human
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176726
VL  - 9
IS  - 1060
ER  - 
TY  - JOUR
A1  - Uri, Anna
A1  - Werner, Sandra
A1  - Lühder, Fred
A1  - Hünig, Thomas
A1  - Kerkau, Thomas
A1  - Beyersdorf, Niklas
T1  - Protection of mice from acute graft-versus-host disease requires CD28 co-stimulation on donor CD4\(^{+}\) Foxp3\(^{+}\) regulatory T Cells
JF  - Frontiers in Immunology
N2  - Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT). In this study, we investigated the requirement for CD28 co-stimulation of donor CD4\(^{+}\) conventional (CD4\(^{+}\)CD25\(^{-}\)Foxp3\(^{-}\), Tconv) and regulatory (CD4\(^{+}\)CD25\(^{+}\)Foxp3\(^{+}\), Treg) T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO) or wild-type (wt) littermates as donors of CD4\(^{+}\) Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4\(^{+}\) Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28 on donor Treg did not abrogate protection of recipient mice from aGvHD until about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg drastically declined as compared to wt Treg. Consequently, only wt, but not CD28-deficient, Treg were able to continuously suppress aGvHD and induce long-term survival of the recipient mice. To our knowledge, this is the first study that specifically evaluates the impact of CD28 expression on donor Treg in aGvHD. Moreover, the delayed kinetics of aGvHD lethality after transplantation of iCD28KO Treg provides a novel animal model for similar disease courses found in patients after allo-HSCT.
KW  - co-stimulation,
KW  - inducible deletion
KW  - regulatory T cells
KW  - acute graft-versus-host disease
KW  - CD28
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158469
VL  - 8
IS  - 721
ER  -