Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+,CD40L+ T cells by producing CCL22

Paolo Ghia, Giuliana Strola, Luisa Granziero, Massimo Geuna, Giuseppe Guida, Federica Sallusto, Nancy Ruffing, Licia Montagna, Paola Piccoli, Marco Chilosi, Federico Caligaris-Cappio

Research output: Contribution to journalArticle

Abstract

The natural history of B-chronic lymphocytic leukemia (CLL) is not entirely explained by intrinsic defects of the neoplastic cell, but is also favored by microenvironmental signals. As CLL cells retain the capacity to respond to CD40 ligand (CD40L) and as CD4+ T cells are always present in involved tissues, we asked whether malignant CLL cells might produce T cell-attracting chemokines. We studied the chemokine expression of CD19+/CD5+ malignant B cells from peripheral blood (PB), lymph nodes (LN) or bone marrow (BM) of 32 patients and found a major difference. LN- and BM-, but not PB-derived cells, expressed a readily detectable reverse transcription-PCR band for CCL22 and one for CCL17 of variable intensity. CD40 ligation of PB cells induced the mRNA expression of both CCL22 and CCL17. CCL22 was also released in the culture supernatants. These supernatants induced the migration of activated CD4+, CD40L+ T cells expressing the CCL22 receptor, CCR4. T cell migration was abrogated by anti-CCL22 antibodies. Immunohistochemistry and cytofluorography studies revealed that a proportion of CD4+ T cells in CLL LN and BM expressed CD40L. Our data demonstrate that malignant CLL cells chemo-attract CD4+ T cells that in turn induce a strong chemokine production by the leukemic clone, suggesting a vicious circle, leading to the progressive accumulation of the neoplastic cells.

Original languageEnglish
Pages (from-to)1403-1413
Number of pages11
JournalEuropean Journal of Immunology
Volume32
Issue number5
DOIs
Publication statusPublished - 2002

Fingerprint

CD40 Ligand
B-Cell Chronic Lymphocytic Leukemia
T-Lymphocytes
Chemokines
Lymph Nodes
Bone Marrow
CCR4 Receptors
Blood Cells
Reverse Transcription
Cell Movement
Ligation
Anti-Idiotypic Antibodies
B-Lymphocytes
Clone Cells
Immunohistochemistry
Polymerase Chain Reaction
Messenger RNA

Keywords

  • CD40L
  • Chemokine
  • Chronic lymphocytic leukemia

ASJC Scopus subject areas

  • Immunology

Cite this

Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+,CD40L+ T cells by producing CCL22. / Ghia, Paolo; Strola, Giuliana; Granziero, Luisa; Geuna, Massimo; Guida, Giuseppe; Sallusto, Federica; Ruffing, Nancy; Montagna, Licia; Piccoli, Paola; Chilosi, Marco; Caligaris-Cappio, Federico.

In: European Journal of Immunology, Vol. 32, No. 5, 2002, p. 1403-1413.

Research output: Contribution to journalArticle

Ghia, P, Strola, G, Granziero, L, Geuna, M, Guida, G, Sallusto, F, Ruffing, N, Montagna, L, Piccoli, P, Chilosi, M & Caligaris-Cappio, F 2002, 'Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+,CD40L+ T cells by producing CCL22', European Journal of Immunology, vol. 32, no. 5, pp. 1403-1413. https://doi.org/10.1002/1521-4141(200205)32:5<1403::AID-IMMU1403>3.0.CO;2-Y
Ghia, Paolo ; Strola, Giuliana ; Granziero, Luisa ; Geuna, Massimo ; Guida, Giuseppe ; Sallusto, Federica ; Ruffing, Nancy ; Montagna, Licia ; Piccoli, Paola ; Chilosi, Marco ; Caligaris-Cappio, Federico. / Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+,CD40L+ T cells by producing CCL22. In: European Journal of Immunology. 2002 ; Vol. 32, No. 5. pp. 1403-1413.
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AU - Ghia, Paolo

AU - Strola, Giuliana

AU - Granziero, Luisa

AU - Geuna, Massimo

AU - Guida, Giuseppe

AU - Sallusto, Federica

AU - Ruffing, Nancy

AU - Montagna, Licia

AU - Piccoli, Paola

AU - Chilosi, Marco

AU - Caligaris-Cappio, Federico

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AB - The natural history of B-chronic lymphocytic leukemia (CLL) is not entirely explained by intrinsic defects of the neoplastic cell, but is also favored by microenvironmental signals. As CLL cells retain the capacity to respond to CD40 ligand (CD40L) and as CD4+ T cells are always present in involved tissues, we asked whether malignant CLL cells might produce T cell-attracting chemokines. We studied the chemokine expression of CD19+/CD5+ malignant B cells from peripheral blood (PB), lymph nodes (LN) or bone marrow (BM) of 32 patients and found a major difference. LN- and BM-, but not PB-derived cells, expressed a readily detectable reverse transcription-PCR band for CCL22 and one for CCL17 of variable intensity. CD40 ligation of PB cells induced the mRNA expression of both CCL22 and CCL17. CCL22 was also released in the culture supernatants. These supernatants induced the migration of activated CD4+, CD40L+ T cells expressing the CCL22 receptor, CCR4. T cell migration was abrogated by anti-CCL22 antibodies. Immunohistochemistry and cytofluorography studies revealed that a proportion of CD4+ T cells in CLL LN and BM expressed CD40L. Our data demonstrate that malignant CLL cells chemo-attract CD4+ T cells that in turn induce a strong chemokine production by the leukemic clone, suggesting a vicious circle, leading to the progressive accumulation of the neoplastic cells.

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