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PI3Kδ Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes.

Pearce VQ, Bouabe H, MacQueen AR, Carbonaro V, Okkenhaug K - J. Immunol. (2015)

Bottom Line: Inactivation of PI3Kδ resulted in enhanced bacterial elimination by the innate immune system.However, the magnitudes of the primary and secondary CD8 +: T cell responses were reduced.Moreover, PI3Kδ activity was required for CD8(+) T cells to provide help to other responding CD8(+) cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom.

No MeSH data available.


Related in: MedlinePlus

CD8 T cell–intrinsic role for p110δ is dose-dependent. The indicated number of purified WT OT1 T cells (CD45.1+) or p110δD910A OT1 T cells (CD45.2+) were transferred into WT recipient mice (CD45.1+CD45.2+), which were infected 1 d later with Lm-OVA and the number of OT1 T cells and endogenous Tet+CD8+ CD8 T cells in the blood was determined by flow cytometry. The left panel shows number of transferred OT1 T cells recovered from blood samples (filled symbols indicate WT OT1; empty symbols indicate p110δD910A OT1). The right panel shows endogenous Tet+CD8+ T cells of WT mice receiving WT OT1 T cells (filled symbols) or p110δD910A OT1 T cells (empty symbols); n = 4–8/group. Results are representative of two to four independent experiments.
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fig05: CD8 T cell–intrinsic role for p110δ is dose-dependent. The indicated number of purified WT OT1 T cells (CD45.1+) or p110δD910A OT1 T cells (CD45.2+) were transferred into WT recipient mice (CD45.1+CD45.2+), which were infected 1 d later with Lm-OVA and the number of OT1 T cells and endogenous Tet+CD8+ CD8 T cells in the blood was determined by flow cytometry. The left panel shows number of transferred OT1 T cells recovered from blood samples (filled symbols indicate WT OT1; empty symbols indicate p110δD910A OT1). The right panel shows endogenous Tet+CD8+ T cells of WT mice receiving WT OT1 T cells (filled symbols) or p110δD910A OT1 T cells (empty symbols); n = 4–8/group. Results are representative of two to four independent experiments.

Mentions: We therefore sought to determine whether PI3Kδ plays a cell-intrinsic role in regulating the expansion of CD8+ T cells following infection in the presence of WT innate immune cells. We started by injecting different numbers of CD45.1+ WT or CD45.2+ p110δD910A Tet+CD8+ T cells expressing the OT1 TCR transgene into WT recipient mice expressing CD45.2 and CD45.1 Ags before infecting recipient mice with Lm-OVA. When 200,000, 1,000, or 500 OT1 T cells were injected, the magnitude of expansion by p110δD910A OT1 T cells was reduced compared with WT OT1 T cells (Fig. 5, left panel). Interestingly, however, when 100 OT1 T cells were injected¸ the difference between the expansion of WT and p110δD910A T cell responses was less noticeable (Fig. 5, left panel), indicating that the function of PI3Kδ is dependent on the size of the responding population.


PI3Kδ Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes.

Pearce VQ, Bouabe H, MacQueen AR, Carbonaro V, Okkenhaug K - J. Immunol. (2015)

CD8 T cell–intrinsic role for p110δ is dose-dependent. The indicated number of purified WT OT1 T cells (CD45.1+) or p110δD910A OT1 T cells (CD45.2+) were transferred into WT recipient mice (CD45.1+CD45.2+), which were infected 1 d later with Lm-OVA and the number of OT1 T cells and endogenous Tet+CD8+ CD8 T cells in the blood was determined by flow cytometry. The left panel shows number of transferred OT1 T cells recovered from blood samples (filled symbols indicate WT OT1; empty symbols indicate p110δD910A OT1). The right panel shows endogenous Tet+CD8+ T cells of WT mice receiving WT OT1 T cells (filled symbols) or p110δD910A OT1 T cells (empty symbols); n = 4–8/group. Results are representative of two to four independent experiments.
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fig05: CD8 T cell–intrinsic role for p110δ is dose-dependent. The indicated number of purified WT OT1 T cells (CD45.1+) or p110δD910A OT1 T cells (CD45.2+) were transferred into WT recipient mice (CD45.1+CD45.2+), which were infected 1 d later with Lm-OVA and the number of OT1 T cells and endogenous Tet+CD8+ CD8 T cells in the blood was determined by flow cytometry. The left panel shows number of transferred OT1 T cells recovered from blood samples (filled symbols indicate WT OT1; empty symbols indicate p110δD910A OT1). The right panel shows endogenous Tet+CD8+ T cells of WT mice receiving WT OT1 T cells (filled symbols) or p110δD910A OT1 T cells (empty symbols); n = 4–8/group. Results are representative of two to four independent experiments.
Mentions: We therefore sought to determine whether PI3Kδ plays a cell-intrinsic role in regulating the expansion of CD8+ T cells following infection in the presence of WT innate immune cells. We started by injecting different numbers of CD45.1+ WT or CD45.2+ p110δD910A Tet+CD8+ T cells expressing the OT1 TCR transgene into WT recipient mice expressing CD45.2 and CD45.1 Ags before infecting recipient mice with Lm-OVA. When 200,000, 1,000, or 500 OT1 T cells were injected, the magnitude of expansion by p110δD910A OT1 T cells was reduced compared with WT OT1 T cells (Fig. 5, left panel). Interestingly, however, when 100 OT1 T cells were injected¸ the difference between the expansion of WT and p110δD910A T cell responses was less noticeable (Fig. 5, left panel), indicating that the function of PI3Kδ is dependent on the size of the responding population.

Bottom Line: Inactivation of PI3Kδ resulted in enhanced bacterial elimination by the innate immune system.However, the magnitudes of the primary and secondary CD8 +: T cell responses were reduced.Moreover, PI3Kδ activity was required for CD8(+) T cells to provide help to other responding CD8(+) cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom.

No MeSH data available.


Related in: MedlinePlus