Cyclophosphamide modulates CD4+ T cells into a T helper type 2 phenotype and reverses increased IFN-γ production of CD8+ T cells in secondary progressive multiple sclerosis

2004 ◽  
Vol 146 (1-2) ◽  
pp. 189-198 ◽  
Author(s):  
Arnon Karni ◽  
Konstantin Balashov ◽  
Wayne W. Hancock ◽  
Padmanabhan Bharanidharan ◽  
Michal Abraham ◽  
...  
2000 ◽  
Vol 191 (5) ◽  
pp. 847-858 ◽  
Author(s):  
Ryuta Nishikomori ◽  
Rolf O. Ehrhardt ◽  
Warren Strober

The differentiation of CD4+ T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor β2 (IL-12Rβ2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rβ2 chain. We reexamined such differentiation using IL-12Rβ2 chain transgenic mice. We found that CD4+ T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-γ production 10–100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12Rβ2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12Rβ2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4–driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-γ production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling.


2007 ◽  
Vol 0 (0) ◽  
pp. 070816152708001-???
Author(s):  
M. W. Kinyanjui ◽  
M. Tamaoka ◽  
E. D. Fixman

Brain ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 916-931 ◽  
Author(s):  
Atsushi Kadowaki ◽  
Ryoko Saga ◽  
Youwei Lin ◽  
Wakiro Sato ◽  
Takashi Yamamura

2013 ◽  
Vol 161 (s2) ◽  
pp. 58-65 ◽  
Author(s):  
Kaori Okuyama ◽  
Masatoshi Suenaga ◽  
Shyunya Furuki ◽  
Tasuku Kawano ◽  
Yuichi Ohkawara ◽  
...  

2007 ◽  
Vol 37 (9) ◽  
pp. 1374-1385 ◽  
Author(s):  
T. Polte ◽  
A. Jagemann ◽  
J. Foell ◽  
R. S. Mittler ◽  
G. Hansen

1995 ◽  
Vol 25 (5) ◽  
pp. 1168-1175 ◽  
Author(s):  
Anne Kelso ◽  
Penny Groves ◽  
Anthony B. Troutt ◽  
Kari Francis

2011 ◽  
Vol 208 (2) ◽  
pp. 369-381 ◽  
Author(s):  
Amariliz Rivera ◽  
Tobias M. Hohl ◽  
Nichole Collins ◽  
Ingrid Leiner ◽  
Alena Gallegos ◽  
...  

Pulmonary infection of mice with Aspergillus fumigatus induces concurrent T helper type 1 (Th1) and Th17 responses that depend on Toll-like receptor/MyD88 and Dectin-1, respectively. However, the mechanisms balancing Th1 and Th17 CD4 T cell populations during infection remain incompletely defined. In this study, we show that Dectin-1 deficiency disproportionally increases Th1 responses and decreases Th17 differentiation after A. fumigatus infection. Dectin-1 signaling in A. fumigatus–infected wild-type mice reduces IFN-γ and IL-12p40 expression in the lung, thereby decreasing T-bet expression in responding CD4 T cells and enhancing Th17 responses. Absence of IFN-γ or IL-12p35 in infected mice or T-bet in responding CD4 T cells enhances Th17 differentiation, independent of Dectin-1 expression, in A. fumigatus–infected mice. Transient deletion of monocyte-derived dendritic cells also reduces Th1 and boosts Th17 differentiation of A. fumigatus–specific CD4 T cells. Our findings indicate that Dectin-1–mediated signals alter CD4 T cell responses to fungal infection by decreasing the production of IL-12 and IFN-γ in innate cells, thereby decreasing T-bet expression in A. fumigatus–specific CD4 T cells and enabling Th17 differentiation.


2002 ◽  
Vol 195 (5) ◽  
pp. 603-616 ◽  
Author(s):  
Franck J. Barrat ◽  
Daniel J. Cua ◽  
André Boonstra ◽  
David F. Richards ◽  
Chad Crain ◽  
...  

We show that a combination of the immunosuppressive drugs, vitamin D3 and Dexamethasone, induced human and mouse naive CD4+ T cells to differentiate in vitro into regulatory T cells. In contrast to the previously described in vitro derived CD4+ T cells, these cells produced only interleukin (IL)-10, but no IL-5 and interferon (IFN)-γ, and furthermore retained strong proliferative capacity. The development of these IL-10–producing cells was enhanced by neutralization of the T helper type 1 (Th1)- and Th2–inducing cytokines IL-4, IL-12, and IFN-γ. These immunosuppressive drugs also induced the development of IL-10–producing T cells in the absence of antigen-presenting cells, with IL-10 acting as a positive autocrine factor for these T cells. Furthermore, nuclear factor (NF)-κB and activator protein (AP)-1 activities were inhibited in the IL-10–producing cells described here as well as key transcription factors involved in Th1 and Th2 subset differentiation. The regulatory function of these in vitro generated IL-10–producing T cells was demonstrated by their ability to prevent central nervous system inflammation, when targeted to the site of inflammation, and this function was shown to be IL-10 dependent. Generating homogeneous populations of IL-10–producing T cells in vitro will thus facilitate the use of regulatory T cells in immunotherapy.


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