TY - JOUR
T1 - IL-7, but not thymic stromal lymphopoietin (TSLP), during priming enhances the generation of memory CD4+ T cells
AU - Guo, Zhiyong
AU - Wang, Guohua
AU - Miyahara, Yoshihiro
AU - Khattar, Mithun
AU - Linkes, Sean P.
AU - Wang, Changxi
AU - Xia, Jiahong
AU - Pan, Yiqing
AU - Chen, Wenhao
AU - He, Xiaoshun
AU - Stepkowski, Stanislaw M.
N1 - Funding Information:
This work was supported by NIH grant HL 69723 .
PY - 2010/2
Y1 - 2010/2
N2 - Multiple activation signals (including antigen, co-stimulation, and cytokines) during T-cell priming affect the subsequent generation of memory T cells, whose survival is maintained by IL-7 and IL-15. Since the IL-7 receptor is highly expressed not only on the surface of memory T cells but also on naïve T cells, we propose that early exposure to IL-7 during priming of naïve T cells may promote their survival, and thus enhances the generation of memory cells. To test this hypothesis, TCR transgenic OT-II CD4+ T cells were stimulated in vitro with OVA323-339 peptide presented by syngeneic antigen-presenting cells (APCs). IL-7 or an IL-7 like cytokine, thymic stromal lymphopoietin (TSLP), was added at the initial 2-day cultivation stage. We found that a short exposure to IL-7 or TSLP during priming did not affect activation, proliferation, and glucose uptake by CD4+ T cells compared to controls when examined on culture day 6. However, the same 6-day cultures showed that IL-7 (but not TSLP) significantly decreased the frequency of apoptotic CD4+ T cells compared to controls. More importantly, an adoptive transfer of the 6-day primed OT-II T cells into CD45.1+ congenic mice demonstrated that IL-7 (but not TSLP) elevated by 3- and 4-fold the number of transferred CD4+ T cells in spleen (p<0.05) and lymph nodes (p<0.05), respectively, compared to controls. Almost all transferred CD4+ T populations displayed phenotypes of effector (CD44+CD62L-) or central (CD44+CD62L+) memory T cells. We thus conclude that exposure of CD4+ T cells to IL-7 during priming results in an increased frequency of CD4+ memory T cells.
AB - Multiple activation signals (including antigen, co-stimulation, and cytokines) during T-cell priming affect the subsequent generation of memory T cells, whose survival is maintained by IL-7 and IL-15. Since the IL-7 receptor is highly expressed not only on the surface of memory T cells but also on naïve T cells, we propose that early exposure to IL-7 during priming of naïve T cells may promote their survival, and thus enhances the generation of memory cells. To test this hypothesis, TCR transgenic OT-II CD4+ T cells were stimulated in vitro with OVA323-339 peptide presented by syngeneic antigen-presenting cells (APCs). IL-7 or an IL-7 like cytokine, thymic stromal lymphopoietin (TSLP), was added at the initial 2-day cultivation stage. We found that a short exposure to IL-7 or TSLP during priming did not affect activation, proliferation, and glucose uptake by CD4+ T cells compared to controls when examined on culture day 6. However, the same 6-day cultures showed that IL-7 (but not TSLP) significantly decreased the frequency of apoptotic CD4+ T cells compared to controls. More importantly, an adoptive transfer of the 6-day primed OT-II T cells into CD45.1+ congenic mice demonstrated that IL-7 (but not TSLP) elevated by 3- and 4-fold the number of transferred CD4+ T cells in spleen (p<0.05) and lymph nodes (p<0.05), respectively, compared to controls. Almost all transferred CD4+ T populations displayed phenotypes of effector (CD44+CD62L-) or central (CD44+CD62L+) memory T cells. We thus conclude that exposure of CD4+ T cells to IL-7 during priming results in an increased frequency of CD4+ memory T cells.
KW - Interleukin 7
KW - Memory T cells
KW - Thymic stromal lymphopoietin
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U2 - 10.1016/j.imlet.2009.12.019
DO - 10.1016/j.imlet.2009.12.019
M3 - Article
C2 - 20064560
AN - SCOPUS:77249166530
SN - 0165-2478
VL - 128
SP - 116
EP - 123
JO - Immunology Letters
JF - Immunology Letters
IS - 2
ER -