IL-7, but not thymic stromal lymphopoietin (TSLP), during priming enhances the generation of memory CD4+ T cells.
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 OVA(323-339) 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.
Guo
Zhiyong
Z
Department of Medical Microbiology and Immunology, University of Toledo Medical College, Toledo, OH 43614, United States.
Wang
Guohua
G
Miyahara
Yoshihiro
Y
Khattar
Mithun
M
Linkes
Sean P
SP
Wang
Changxi
C
Xia
Jiahong
J
Pan
Yiqing
Y
Chen
Wenhao
W
He
Xiaoshun
X
Stepkowski
Stanislaw M
SM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D015851:Interleukin-7; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse