TY - JOUR
T1 - B7-H4-Ig treatment of normal mice changes lymphocyte homeostasis and increases the potential of regulatory T cells
AU - Kristensen, Nanna N
AU - Schmidt, Esben G W
AU - Rasmussen, Susanne
AU - Balk-Møller, Emilie
AU - Claesson, Mogens Helweg
PY - 2013/8
Y1 - 2013/8
N2 - Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed by professional antigen-presenting cells. By delivering signal 2 during T cell activation, it inhibits T cell proliferation and inflammation. In this study, we have used a newly developed B7-H4-Ig fusion protein and evaluated its effect on eAg-activated effector and regulatory T cells (Treg) in vitro and in vivo. T cells were recovered from the mesenteric lymph nodes (MLNs) of untreated or B7-H4-Ig-treated BALB/c mice. Treatment of cells in vitro did neither affect the proliferation of effector T cells nor the function of Tregs. In vivo, B7-H4 treatment increased the total number of MLN-derived CD4⁺ and CD8⁺ T cell subsets as well as the functional activity of MLN-derived Tregs, whereas the proliferative activity of eAg or alloantigen specific effector T cells was not influenced, although treatment resulted in less secretion of inflammatory cytokines and chemokines from these cells. B7-H4-Ig treatment of severe combined immune-deficient (SCID) mice undergoing T cell transfer colitis did not influence the course of disease probably reflecting the lack of Tregs in this model of chronic colitis. In conclusion, we show that treatment with B7-H4-Ig in vivo changes lymphocyte homeostasis and increases the regulatory potential in normal mice, but does not affect the course of disease development in SCID mice undergoing T cell transfer colitis.
AB - Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed by professional antigen-presenting cells. By delivering signal 2 during T cell activation, it inhibits T cell proliferation and inflammation. In this study, we have used a newly developed B7-H4-Ig fusion protein and evaluated its effect on eAg-activated effector and regulatory T cells (Treg) in vitro and in vivo. T cells were recovered from the mesenteric lymph nodes (MLNs) of untreated or B7-H4-Ig-treated BALB/c mice. Treatment of cells in vitro did neither affect the proliferation of effector T cells nor the function of Tregs. In vivo, B7-H4 treatment increased the total number of MLN-derived CD4⁺ and CD8⁺ T cell subsets as well as the functional activity of MLN-derived Tregs, whereas the proliferative activity of eAg or alloantigen specific effector T cells was not influenced, although treatment resulted in less secretion of inflammatory cytokines and chemokines from these cells. B7-H4-Ig treatment of severe combined immune-deficient (SCID) mice undergoing T cell transfer colitis did not influence the course of disease probably reflecting the lack of Tregs in this model of chronic colitis. In conclusion, we show that treatment with B7-H4-Ig in vivo changes lymphocyte homeostasis and increases the regulatory potential in normal mice, but does not affect the course of disease development in SCID mice undergoing T cell transfer colitis.
U2 - 10.3109/08923973.2013.810642
DO - 10.3109/08923973.2013.810642
M3 - Journal article
C2 - 23841452
SN - 0892-3973
VL - 35
SP - 505
EP - 513
JO - Immunopharmacology and Immunotoxicology
JF - Immunopharmacology and Immunotoxicology
IS - 4
ER -