CCL16 enhances the CD8+ and CD4+ T cell reactivity to human HER-2 elicited by dendritic cells loaded with rat ortholog HER-2.
T cells from HLA-A2+ healthy donors were co-cultured with autologous dendritic cells (DC) loaded with apoptotic tumor cells expressing rat neu, and were induced to mature by tumor necrosis factor (TNF)alpha and interleukin (IL)-1beta (mDC(neu)) or by the CCL16 chemokine (CCL16/mDC(neu)). Priming by CCL16/mDC(neu) induces a larger population of T cells that express cytoplasmatic interferon (IFN)gamma, TNFalpha, perforin and granzyme B compared to those primed by mDC(neu). T cells primed by CCL16/mDC(neu) release IFNgamma in response to human HER-2+ cells and kill human HER-2+ target cells more efficiently than those primed by mDC(neu). Our results show that both the loading of DC with xenogeneic rat neu and their maturation by CCL16 are two issues of critical importance for the elicitation of an effective response to human HER-2 in T cells from normal donors.
Caorsi
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C
Department of Medicine and Experimental Oncology, University of Turin, Turin, Italy.
Cappello
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P
Ceruti
P
P
Amici
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A
Marchini
C
C
Novelli
F
F
Forni
G
G
Giovarelli
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D019742:Chemokines, CC / Q000502:physiology*; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
D019742:Chemokines, CC; D018719:Erb-b2 Receptor Tyrosine Kinases; C481939:CCL16 protein, human