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Interleukin 15 controls both proliferation and survival of a subset of memory-phenotype CD8(+) T cells.

Judge AD, Zhang X, Fujii H, Surh CD, Sprent J - J. Exp. Med. (2002)

Bottom Line: Here, evidence is presented that CD44(hi) CD8(+) cells comprise a mixed population of IL-15-dependent and IL-15-independent cells.In contrast to CD122(hi) cells, the CD122(lo) subset of CD44(hi) CD8(+) cells is IL-15 independent; likewise, being CD122(lo), CD44(hi) CD4(+) cells are IL-15 independent.Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

ABSTRACT
Previous work has shown that memory-phenotype CD44(hi) CD8(+) cells are controlled by a cytokine, interleukin (IL)-15. However, the dependency of CD44(hi) CD8(+) cells on IL-15 is partial rather than complete. Here, evidence is presented that CD44(hi) CD8(+) cells comprise a mixed population of IL-15-dependent and IL-15-independent cells. The major subset of CD122(hi) CD44(hi) CD8(+) cells is heavily dependent on IL-15 by three different parameters, namely (1) "bystander" proliferation induced via IFN-induced stimulation of the innate immune system, (2) normal "background" proliferation, and (3) T cell survival; IL-15 dependency is most extreme for the Ly49(+) subset of CD122(hi) CD44(hi) CD8(+) cells. In contrast to CD122(hi) cells, the CD122(lo) subset of CD44(hi) CD8(+) cells is IL-15 independent; likewise, being CD122(lo), CD44(hi) CD4(+) cells are IL-15 independent. Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.

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A subset of CD44hi CD8+ T cells is IL-15 dependent. (a) Histograms show expression of CD44 on gated CD8+ cells and CD122 on gated CD8+ and CD44hi CD8+ cells from LN of wild-type B6 versus IL-15−/− mice. (b–h) The data show CD122 or Ly49 versus CD44 expression on gated CD8+ LN T cells from wild-type B6 mice (b–d), IL-15−/− mice (e and f), CD122−/− mice (g), and IL-2−/− mice (h). The data are representative of >4 mice (aged 2–3 mo)/group and also applied to CD8+ spleen and peripheral blood cells (not shown). In d, data refer to gated Ly49+ CD8+ T cells. In all groups, Ly49 was detected using a panel of anti-Ly49A, C/I, F, and G2 mAbs that have previously been shown to be the most abundantly expressed Ly49 family members on CD8+ T cells in B6 mice (reference 20).
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fig2: A subset of CD44hi CD8+ T cells is IL-15 dependent. (a) Histograms show expression of CD44 on gated CD8+ cells and CD122 on gated CD8+ and CD44hi CD8+ cells from LN of wild-type B6 versus IL-15−/− mice. (b–h) The data show CD122 or Ly49 versus CD44 expression on gated CD8+ LN T cells from wild-type B6 mice (b–d), IL-15−/− mice (e and f), CD122−/− mice (g), and IL-2−/− mice (h). The data are representative of >4 mice (aged 2–3 mo)/group and also applied to CD8+ spleen and peripheral blood cells (not shown). In d, data refer to gated Ly49+ CD8+ T cells. In all groups, Ly49 was detected using a panel of anti-Ly49A, C/I, F, and G2 mAbs that have previously been shown to be the most abundantly expressed Ly49 family members on CD8+ T cells in B6 mice (reference 20).

Mentions: As mentioned above, CD44hi CD8+ cells express much higher levels of CD122 (an important component of the IL-15 receptor) than CD44hi CD4+ cells (15, 18). However, CD122 expression on CD44hi CD8+ cells is heterogeneous, ∼60% of these cells being CD122hi in young mice and the remainder being CD122lo (Fig. 2 , a and b). Confirming the results of others (20), a subset (20–30%) of CD122hi CD8+ cells resembles NK cells in expressing high levels of the Ly49 marker (Fig. 2 c, see Figure legend for detecting Ly49 expression). Virtually all Ly49+ CD8+ cells are CD122hi CD44hi (Fig. 2 d).


Interleukin 15 controls both proliferation and survival of a subset of memory-phenotype CD8(+) T cells.

Judge AD, Zhang X, Fujii H, Surh CD, Sprent J - J. Exp. Med. (2002)

A subset of CD44hi CD8+ T cells is IL-15 dependent. (a) Histograms show expression of CD44 on gated CD8+ cells and CD122 on gated CD8+ and CD44hi CD8+ cells from LN of wild-type B6 versus IL-15−/− mice. (b–h) The data show CD122 or Ly49 versus CD44 expression on gated CD8+ LN T cells from wild-type B6 mice (b–d), IL-15−/− mice (e and f), CD122−/− mice (g), and IL-2−/− mice (h). The data are representative of >4 mice (aged 2–3 mo)/group and also applied to CD8+ spleen and peripheral blood cells (not shown). In d, data refer to gated Ly49+ CD8+ T cells. In all groups, Ly49 was detected using a panel of anti-Ly49A, C/I, F, and G2 mAbs that have previously been shown to be the most abundantly expressed Ly49 family members on CD8+ T cells in B6 mice (reference 20).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194030&req=5

fig2: A subset of CD44hi CD8+ T cells is IL-15 dependent. (a) Histograms show expression of CD44 on gated CD8+ cells and CD122 on gated CD8+ and CD44hi CD8+ cells from LN of wild-type B6 versus IL-15−/− mice. (b–h) The data show CD122 or Ly49 versus CD44 expression on gated CD8+ LN T cells from wild-type B6 mice (b–d), IL-15−/− mice (e and f), CD122−/− mice (g), and IL-2−/− mice (h). The data are representative of >4 mice (aged 2–3 mo)/group and also applied to CD8+ spleen and peripheral blood cells (not shown). In d, data refer to gated Ly49+ CD8+ T cells. In all groups, Ly49 was detected using a panel of anti-Ly49A, C/I, F, and G2 mAbs that have previously been shown to be the most abundantly expressed Ly49 family members on CD8+ T cells in B6 mice (reference 20).
Mentions: As mentioned above, CD44hi CD8+ cells express much higher levels of CD122 (an important component of the IL-15 receptor) than CD44hi CD4+ cells (15, 18). However, CD122 expression on CD44hi CD8+ cells is heterogeneous, ∼60% of these cells being CD122hi in young mice and the remainder being CD122lo (Fig. 2 , a and b). Confirming the results of others (20), a subset (20–30%) of CD122hi CD8+ cells resembles NK cells in expressing high levels of the Ly49 marker (Fig. 2 c, see Figure legend for detecting Ly49 expression). Virtually all Ly49+ CD8+ cells are CD122hi CD44hi (Fig. 2 d).

Bottom Line: Here, evidence is presented that CD44(hi) CD8(+) cells comprise a mixed population of IL-15-dependent and IL-15-independent cells.In contrast to CD122(hi) cells, the CD122(lo) subset of CD44(hi) CD8(+) cells is IL-15 independent; likewise, being CD122(lo), CD44(hi) CD4(+) cells are IL-15 independent.Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

ABSTRACT
Previous work has shown that memory-phenotype CD44(hi) CD8(+) cells are controlled by a cytokine, interleukin (IL)-15. However, the dependency of CD44(hi) CD8(+) cells on IL-15 is partial rather than complete. Here, evidence is presented that CD44(hi) CD8(+) cells comprise a mixed population of IL-15-dependent and IL-15-independent cells. The major subset of CD122(hi) CD44(hi) CD8(+) cells is heavily dependent on IL-15 by three different parameters, namely (1) "bystander" proliferation induced via IFN-induced stimulation of the innate immune system, (2) normal "background" proliferation, and (3) T cell survival; IL-15 dependency is most extreme for the Ly49(+) subset of CD122(hi) CD44(hi) CD8(+) cells. In contrast to CD122(hi) cells, the CD122(lo) subset of CD44(hi) CD8(+) cells is IL-15 independent; likewise, being CD122(lo), CD44(hi) CD4(+) cells are IL-15 independent. Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.

Show MeSH
Related in: MedlinePlus