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The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand.

Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ - J. Exp. Med. (1997)

Bottom Line: They express CD45RA, but not markers specific for known lymphoid- or myeloid-derived cell types.They undergo rapid apoptosis in culture, unless rescued by IL-3.Further addition of CD40-ligand results in their differentiation into dendritic cells that express low levels of myeloid antigens CD13 and CD33.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.

ABSTRACT
A subset of CD4+CD11c-CD3- blood cells was recently shown to develop into dendritic cells when cultured with monocyte conditioned medium. Here, we demonstrate that CD4+ CD11c-CD3- cells, isolated from tonsils, correspond to the so-called plasmacytoid T cells, an obscure cell type that has long been observed by pathologists within secondary lymphoid tissues. They express CD45RA, but not markers specific for known lymphoid- or myeloid-derived cell types. They undergo rapid apoptosis in culture, unless rescued by IL-3. Further addition of CD40-ligand results in their differentiation into dendritic cells that express low levels of myeloid antigens CD13 and CD33.

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CD4+CD11c−CD3− plasmacytoid cells undergo rapid apoptosis when cultured in medium, unless rescued by IL-3. (A) Many cell clusters at  4 h of culture with IL-3; (B) Dispersed cells at 4 h of culture in medium alone; (C) Few apoptotic cells within clusters at 4 h of culture with IL-3; (D)  Many apoptotic cells at 4 h of culture in medium alone; (E) Cells display pseudopods at 16 h of culture with IL-3; (F). All cells are dead at 16 h of culture  in medium; (G) Mitotic figures at 3 d of culture with IL-3; (H) cells with pseudopods at 6 d of culture with IL-3. Data shown are one representative of  six experiments. Original magnification: (B) ×200.
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Figure 5: CD4+CD11c−CD3− plasmacytoid cells undergo rapid apoptosis when cultured in medium, unless rescued by IL-3. (A) Many cell clusters at 4 h of culture with IL-3; (B) Dispersed cells at 4 h of culture in medium alone; (C) Few apoptotic cells within clusters at 4 h of culture with IL-3; (D) Many apoptotic cells at 4 h of culture in medium alone; (E) Cells display pseudopods at 16 h of culture with IL-3; (F). All cells are dead at 16 h of culture in medium; (G) Mitotic figures at 3 d of culture with IL-3; (H) cells with pseudopods at 6 d of culture with IL-3. Data shown are one representative of six experiments. Original magnification: (B) ×200.

Mentions: The nature of these plasmacytoid cells was further analyzed by cell culture with different cytokines. Strikingly, these cells undergo rapid spontaneous apoptosis in culture, resulting in 40% of cells displaying apoptotic figures at 4 h (Fig. 5, B and D) and >90% at 16 h (Fig. 5 F). Among a wide range of tested cytokines (IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, M-CSF, GM-CSF, SCF) and CD40-ligand, IL-3 alone was found to completely block the apoptotic cell death of plasmacytoid cells (Fig. 5, A and C). In contrast to cells cultured in medium alone, cells cultured with IL-3 rapidly formed aggregates within 4 h (Fig. 5 A) and few cells displayed apoptotic figures (Fig. 5 C). During the next 6 d of culture with IL-3, >90% of cells remained viable (Fig. 6 A) and displayed: (a) pseudopods after 16 h of culture (Fig. 5 E); (b) blastic nuclei and mitotic figures after 3 d of culture (Fig. 5 G); and (c) veiled morphology after 6 d of culture (Fig. 5 H). The CD4+ plasmacytoid cells cultured for 3 d in the presence of IL-3 incorporated [3H]thymidine (Fig. 6 B), a finding consistent with the appearance of mitotic figures at this stage. Two cytokine combinations (GM-CSF+TNFα and GM-CSF+IL-4) that, respectively, induce CD34+ progenitor cells (13) and blood monocytes (11) to become DC did not have significant survival (not shown) and proliferation (Fig. 6 B) effects on plasmacytoid cells. CD40-ligand, a key survival and activation signal for several cell types (16–18), including B cells (19, 20) and DC (21), did not interfere with the IL-3–dependent survival of plasmacytoid cells, but inhibited the IL-3–dependent [3H]thymidine uptake (Fig. 6 B).


The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand.

Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ - J. Exp. Med. (1997)

CD4+CD11c−CD3− plasmacytoid cells undergo rapid apoptosis when cultured in medium, unless rescued by IL-3. (A) Many cell clusters at  4 h of culture with IL-3; (B) Dispersed cells at 4 h of culture in medium alone; (C) Few apoptotic cells within clusters at 4 h of culture with IL-3; (D)  Many apoptotic cells at 4 h of culture in medium alone; (E) Cells display pseudopods at 16 h of culture with IL-3; (F). All cells are dead at 16 h of culture  in medium; (G) Mitotic figures at 3 d of culture with IL-3; (H) cells with pseudopods at 6 d of culture with IL-3. Data shown are one representative of  six experiments. Original magnification: (B) ×200.
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Related In: Results  -  Collection

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Figure 5: CD4+CD11c−CD3− plasmacytoid cells undergo rapid apoptosis when cultured in medium, unless rescued by IL-3. (A) Many cell clusters at 4 h of culture with IL-3; (B) Dispersed cells at 4 h of culture in medium alone; (C) Few apoptotic cells within clusters at 4 h of culture with IL-3; (D) Many apoptotic cells at 4 h of culture in medium alone; (E) Cells display pseudopods at 16 h of culture with IL-3; (F). All cells are dead at 16 h of culture in medium; (G) Mitotic figures at 3 d of culture with IL-3; (H) cells with pseudopods at 6 d of culture with IL-3. Data shown are one representative of six experiments. Original magnification: (B) ×200.
Mentions: The nature of these plasmacytoid cells was further analyzed by cell culture with different cytokines. Strikingly, these cells undergo rapid spontaneous apoptosis in culture, resulting in 40% of cells displaying apoptotic figures at 4 h (Fig. 5, B and D) and >90% at 16 h (Fig. 5 F). Among a wide range of tested cytokines (IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, M-CSF, GM-CSF, SCF) and CD40-ligand, IL-3 alone was found to completely block the apoptotic cell death of plasmacytoid cells (Fig. 5, A and C). In contrast to cells cultured in medium alone, cells cultured with IL-3 rapidly formed aggregates within 4 h (Fig. 5 A) and few cells displayed apoptotic figures (Fig. 5 C). During the next 6 d of culture with IL-3, >90% of cells remained viable (Fig. 6 A) and displayed: (a) pseudopods after 16 h of culture (Fig. 5 E); (b) blastic nuclei and mitotic figures after 3 d of culture (Fig. 5 G); and (c) veiled morphology after 6 d of culture (Fig. 5 H). The CD4+ plasmacytoid cells cultured for 3 d in the presence of IL-3 incorporated [3H]thymidine (Fig. 6 B), a finding consistent with the appearance of mitotic figures at this stage. Two cytokine combinations (GM-CSF+TNFα and GM-CSF+IL-4) that, respectively, induce CD34+ progenitor cells (13) and blood monocytes (11) to become DC did not have significant survival (not shown) and proliferation (Fig. 6 B) effects on plasmacytoid cells. CD40-ligand, a key survival and activation signal for several cell types (16–18), including B cells (19, 20) and DC (21), did not interfere with the IL-3–dependent survival of plasmacytoid cells, but inhibited the IL-3–dependent [3H]thymidine uptake (Fig. 6 B).

Bottom Line: They express CD45RA, but not markers specific for known lymphoid- or myeloid-derived cell types.They undergo rapid apoptosis in culture, unless rescued by IL-3.Further addition of CD40-ligand results in their differentiation into dendritic cells that express low levels of myeloid antigens CD13 and CD33.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.

ABSTRACT
A subset of CD4+CD11c-CD3- blood cells was recently shown to develop into dendritic cells when cultured with monocyte conditioned medium. Here, we demonstrate that CD4+ CD11c-CD3- cells, isolated from tonsils, correspond to the so-called plasmacytoid T cells, an obscure cell type that has long been observed by pathologists within secondary lymphoid tissues. They express CD45RA, but not markers specific for known lymphoid- or myeloid-derived cell types. They undergo rapid apoptosis in culture, unless rescued by IL-3. Further addition of CD40-ligand results in their differentiation into dendritic cells that express low levels of myeloid antigens CD13 and CD33.

Show MeSH