Defective lymphokine production by most CD8+ and CD4+ tumor-specific T cell clones derived from human melanoma-infiltrating lymphocytes in response to autologous tumor cellsin vitro - Archive ouverte HAL Access content directly
Journal Articles European Journal of Immunology Year : 1994

Defective lymphokine production by most CD8+ and CD4+ tumor-specific T cell clones derived from human melanoma-infiltrating lymphocytes in response to autologous tumor cellsin vitro

(1) , (1) , (1) , (1) , (1) , (1) , (1)
1

Abstract

Human melanomas are infiltrated by tumor-reactive T lymphocytes. However, the ability of these cells to elicit a specific anti-tumor response in vivo remains to be established. Because lymphokine production is critical for T cell functions, we have analyzed the capacity of melanoma-specific tumor-infiltrating lymphocyte (TIL) clones to produce major lymphokines: interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), as well as tumor necrosis factor (TNF), in response to direct antigen presentation by autologous and allogeneic tumor cells. We report here that, upon stimulation by autologous melanoma cells, all TIL clones secreted TNF but only a few of them produced significant amounts of IL-2, IL-4 or IFN-gamma. Nonetheless, all these clones consistently produced two or three of these last lymphokines upon stimulation with phorbol myristate acetate and calcium ionophore, as well as IL-2 upon CD3 stimulation, showing the existence of three lymphokine profiles among them: Th1, Th0 and a profile characterized by IL-2 and IL-4, but not IFN-gamma secretion. Stimulation of TIL clones by allogeneic melanoma lines sharing the appropriate HLA-peptide complexes revealed that defective IL-2 production seemed to be a constant feature for some clones, while it was, for other clones, dependent on the antigen-presenting tumor cells. For this last type of clone, we further showed that defective IL-2 induction resulted from an LFA-3 defect of some melanoma cells or from distinct yet undefined defects of other melanoma lines. Our data suggest that defective lymphokine secretion may be an essential component of the in vivo failure of melanoma-reactive TIL to control tumor development. Interestingly both CD4+ and CD8+ TIL clones from one patient were fully activated by the autologous melanoma cells in vitro, supporting a potential role of such TIL in spontaneous or induced tumor rejection.
Fichier principal
Vignette du fichier
eji.1830240905.pdf (1.35 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

inserm-03350944 , version 1 (21-09-2021)

Identifiers

Cite

Yannick Guilloux, Christophe Viret, Nadine Gervois, Eric Le Dréan, Marie-Christine Pandolfino, et al.. Defective lymphokine production by most CD8+ and CD4+ tumor-specific T cell clones derived from human melanoma-infiltrating lymphocytes in response to autologous tumor cellsin vitro. European Journal of Immunology, 1994, 24 (9), pp.1966-1973. ⟨10.1002/eji.1830240905⟩. ⟨inserm-03350944⟩

Collections

INSERM
22 View
20 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More