Limits...
IL-7 promotes the transition of CD4 effectors to persistent memory cells.

Li J, Huston G, Swain SL - J. Exp. Med. (2003)

Bottom Line: After transfer to adoptive hosts, in vitro-generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown.When in vitro-generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype.These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.

View Article: PubMed Central - PubMed

Affiliation: Trudeau Institute, Inc, Saranac Lake, NY 12983, USA.

ABSTRACT
After transfer to adoptive hosts, in vitro-generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown. We find that low doses of interleukin (IL) 7 enhance survival of effectors in vitro without driving their division. When in vitro-generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype. CD4 effectors generated from wild-type versus IL-7 receptor-/- mice were transferred to adoptive hosts, including intact mice and those deficient in IL-7. In each case, the response to IL-7 was critical for good recovery of donor cells after 5-7 d. Recovery was also IL-7-dependent in Class II hosts where division was minimal. Blocking antibodies to IL-7 dramatically decreased short-term recovery of transferred effectors in vivo without affecting their division. These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.

Show MeSH

Related in: MedlinePlus

Effector cells that lack IL-7 response or are transferred to IL-7–deficient hosts survive poorly. (a) Transfer of effectors deficient in IL-7R expression. In vitro–generated AND IL-7R−/− Th2 effector cells (Thy1.2) and WT AND Th2 effector cells (GFP+, Thy1.2) were mixed in equal proportions and injected into ATXBM hosts (Thy1.1) (left). middle, Class II KO hosts. right, intact hosts. After 4–7 d, spleen and lymph node cells were recovered and the percentage of the donor cells that were WT (GFP+, Thy1.2) versus IL-7R−/− (GFP−, Thy1.2) is shown. Data are the means of three mice per group, with standard deviation. Similar effects were seen in two replicate experiments. (b) Effectors divide less and survive less well in IL-7–deficient hosts (left). WT in vitro–generated Th2 effectors were CFSE-labeled and transferred to groups of hosts, including IL-7−/−, IL-7R−/−, and Rag-2 KO mice. The number of donor cells recovered were determined by gating on CD4-CYC and Thy1.1-PE. Donor cell recovery at day 5 from the experiment described in panel a is shown (left). Similar reduction in the recovery of donor cells in IL-7−/− compared with IL-7R−/− was seen in the other experiments and at days 2 and 7 and at 6 mo. Results are representative of three separate experiments. Bcl-2 expression in different hosts (right). In the same experimental design, Th2 effectors (Thy1.1) were transferred into IL-7−/−, IL-7R−/−, and Rag-2−/− hosts. Cells were recovered from the pooled spleen and lymph node at day 4 after transfer. Donor cell Bcl-2 expression was determined by intracellular staining with Ab to Bcl-2. Isotype control Ab staining (not depicted) was below 10 mean index of fluorescence in cells recovered from each host.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2194161&req=5

fig3: Effector cells that lack IL-7 response or are transferred to IL-7–deficient hosts survive poorly. (a) Transfer of effectors deficient in IL-7R expression. In vitro–generated AND IL-7R−/− Th2 effector cells (Thy1.2) and WT AND Th2 effector cells (GFP+, Thy1.2) were mixed in equal proportions and injected into ATXBM hosts (Thy1.1) (left). middle, Class II KO hosts. right, intact hosts. After 4–7 d, spleen and lymph node cells were recovered and the percentage of the donor cells that were WT (GFP+, Thy1.2) versus IL-7R−/− (GFP−, Thy1.2) is shown. Data are the means of three mice per group, with standard deviation. Similar effects were seen in two replicate experiments. (b) Effectors divide less and survive less well in IL-7–deficient hosts (left). WT in vitro–generated Th2 effectors were CFSE-labeled and transferred to groups of hosts, including IL-7−/−, IL-7R−/−, and Rag-2 KO mice. The number of donor cells recovered were determined by gating on CD4-CYC and Thy1.1-PE. Donor cell recovery at day 5 from the experiment described in panel a is shown (left). Similar reduction in the recovery of donor cells in IL-7−/− compared with IL-7R−/− was seen in the other experiments and at days 2 and 7 and at 6 mo. Results are representative of three separate experiments. Bcl-2 expression in different hosts (right). In the same experimental design, Th2 effectors (Thy1.1) were transferred into IL-7−/−, IL-7R−/−, and Rag-2−/− hosts. Cells were recovered from the pooled spleen and lymph node at day 4 after transfer. Donor cell Bcl-2 expression was determined by intracellular staining with Ab to Bcl-2. Isotype control Ab staining (not depicted) was below 10 mean index of fluorescence in cells recovered from each host.

Mentions: Th2 effectors generated from WT and IL-7R−/− AND TCR Tg mice were transferred to adoptive hosts, and their survival was compared (Fig. 3 a). To better understand the mechanisms of any IL-7 effects we might see, we compared intact hosts, ATXBM hosts (which lack T cells and are, thus, somewhat lymphopenic and may undergo enhanced HDD), and Class II KO hosts in which the effectors cannot recognize major histocompatibility molecules (2) and, therefore, do not undergo TCR–Class II interaction–dependent HDD.


IL-7 promotes the transition of CD4 effectors to persistent memory cells.

Li J, Huston G, Swain SL - J. Exp. Med. (2003)

Effector cells that lack IL-7 response or are transferred to IL-7–deficient hosts survive poorly. (a) Transfer of effectors deficient in IL-7R expression. In vitro–generated AND IL-7R−/− Th2 effector cells (Thy1.2) and WT AND Th2 effector cells (GFP+, Thy1.2) were mixed in equal proportions and injected into ATXBM hosts (Thy1.1) (left). middle, Class II KO hosts. right, intact hosts. After 4–7 d, spleen and lymph node cells were recovered and the percentage of the donor cells that were WT (GFP+, Thy1.2) versus IL-7R−/− (GFP−, Thy1.2) is shown. Data are the means of three mice per group, with standard deviation. Similar effects were seen in two replicate experiments. (b) Effectors divide less and survive less well in IL-7–deficient hosts (left). WT in vitro–generated Th2 effectors were CFSE-labeled and transferred to groups of hosts, including IL-7−/−, IL-7R−/−, and Rag-2 KO mice. The number of donor cells recovered were determined by gating on CD4-CYC and Thy1.1-PE. Donor cell recovery at day 5 from the experiment described in panel a is shown (left). Similar reduction in the recovery of donor cells in IL-7−/− compared with IL-7R−/− was seen in the other experiments and at days 2 and 7 and at 6 mo. Results are representative of three separate experiments. Bcl-2 expression in different hosts (right). In the same experimental design, Th2 effectors (Thy1.1) were transferred into IL-7−/−, IL-7R−/−, and Rag-2−/− hosts. Cells were recovered from the pooled spleen and lymph node at day 4 after transfer. Donor cell Bcl-2 expression was determined by intracellular staining with Ab to Bcl-2. Isotype control Ab staining (not depicted) was below 10 mean index of fluorescence in cells recovered from each host.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194161&req=5

fig3: Effector cells that lack IL-7 response or are transferred to IL-7–deficient hosts survive poorly. (a) Transfer of effectors deficient in IL-7R expression. In vitro–generated AND IL-7R−/− Th2 effector cells (Thy1.2) and WT AND Th2 effector cells (GFP+, Thy1.2) were mixed in equal proportions and injected into ATXBM hosts (Thy1.1) (left). middle, Class II KO hosts. right, intact hosts. After 4–7 d, spleen and lymph node cells were recovered and the percentage of the donor cells that were WT (GFP+, Thy1.2) versus IL-7R−/− (GFP−, Thy1.2) is shown. Data are the means of three mice per group, with standard deviation. Similar effects were seen in two replicate experiments. (b) Effectors divide less and survive less well in IL-7–deficient hosts (left). WT in vitro–generated Th2 effectors were CFSE-labeled and transferred to groups of hosts, including IL-7−/−, IL-7R−/−, and Rag-2 KO mice. The number of donor cells recovered were determined by gating on CD4-CYC and Thy1.1-PE. Donor cell recovery at day 5 from the experiment described in panel a is shown (left). Similar reduction in the recovery of donor cells in IL-7−/− compared with IL-7R−/− was seen in the other experiments and at days 2 and 7 and at 6 mo. Results are representative of three separate experiments. Bcl-2 expression in different hosts (right). In the same experimental design, Th2 effectors (Thy1.1) were transferred into IL-7−/−, IL-7R−/−, and Rag-2−/− hosts. Cells were recovered from the pooled spleen and lymph node at day 4 after transfer. Donor cell Bcl-2 expression was determined by intracellular staining with Ab to Bcl-2. Isotype control Ab staining (not depicted) was below 10 mean index of fluorescence in cells recovered from each host.
Mentions: Th2 effectors generated from WT and IL-7R−/− AND TCR Tg mice were transferred to adoptive hosts, and their survival was compared (Fig. 3 a). To better understand the mechanisms of any IL-7 effects we might see, we compared intact hosts, ATXBM hosts (which lack T cells and are, thus, somewhat lymphopenic and may undergo enhanced HDD), and Class II KO hosts in which the effectors cannot recognize major histocompatibility molecules (2) and, therefore, do not undergo TCR–Class II interaction–dependent HDD.

Bottom Line: After transfer to adoptive hosts, in vitro-generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown.When in vitro-generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype.These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.

View Article: PubMed Central - PubMed

Affiliation: Trudeau Institute, Inc, Saranac Lake, NY 12983, USA.

ABSTRACT
After transfer to adoptive hosts, in vitro-generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown. We find that low doses of interleukin (IL) 7 enhance survival of effectors in vitro without driving their division. When in vitro-generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype. CD4 effectors generated from wild-type versus IL-7 receptor-/- mice were transferred to adoptive hosts, including intact mice and those deficient in IL-7. In each case, the response to IL-7 was critical for good recovery of donor cells after 5-7 d. Recovery was also IL-7-dependent in Class II hosts where division was minimal. Blocking antibodies to IL-7 dramatically decreased short-term recovery of transferred effectors in vivo without affecting their division. These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.

Show MeSH
Related in: MedlinePlus