Augmentation of monocyte interleukin‐8 production by psoralen/UVA‐treated CD4⁺ T cells

Abstract

Treatment of cells with psoralen and ultraviolet A light (UVA) modulates their cytokine production. As extracorporeal photochemotherapy has been reported to induce cytokine production by monocytes, we quantified interleukin-8 (IL-8), a representative chemokine produced by monocytes, in culture supernatants from human peripheral blood mononuclear cells (PBMC) treated with 8-methoxypsoralen (8-MOP) and UVA. Lipopolysaccharide stimulated IL-8 production in 8-MOP-phototreated PBMC more efficiently than those untreated or treated with 8-MOP or UVA. More interestingly, when cultured with T-cell-stimulating anti-CD3 and anti-CD28 antibodies, 8-MOP/UVA-treated PBMC produced enhanced amounts of IL-8 with an increased level of IL-8 mRNA expression. Depletion of CD4 but not CD8 T cells from PBMC abrogated this augmented IL-8 elaboration, and CD4 T cells per se secreted no substantial amount of IL-8 even upon CD3/CD28 stimulation. Thus, 8-MOP/UVA-treated CD4 T cells stimulated monocytes to secrete IL-8. The IL-8 overproduction was induced by direct contact of monocytes with 8-MOP/UVA-treated CD4 T cells but not by cytokines from the treated CD4 T cells. These findings imply that in extracorporeal photochemotherapy, monocytes effectively produce IL-8 by cell-to-cell contact with 8-MOP/UVA-treated malignant CD4 T cells. The augmentation of monocyte cytokine/chemokine production by 8-MOP/UVA may be one of the mechanisms underlying the therapeutic efficacy of extracorporeal photochemotherapy.

Extracorporeal photopheresis: A focus on apoptosis and cytokines

“…In an in vitro model, 8-MOP/UVA treated CD4 + T cells enhanced IL8 secretion in monocytes through a cell-cell contact process [74]. The released IL8 may allow CD8 + T cells to gather round the now tumourantigen bearing DCs, generated post-ECP, leading to the induction or activation of tumoricidal Tcells [75].…”

Myeloid Cells as Targets for Therapy in Solid Tumors

“…33 On the other hand, therapeutic efficacy of extracorporeal photochemotherapy involves CD4 + T cell–induced secretion of monocyte-derived IL-8. 82 In addition to fostering T cell chemotaxis, IL-8 suppresses CD4 + T cell–derived IL-4, 83 thus indicating that cross-talk between CD4 + T cells and myeloid cells can modulate humoral versus cell-mediated responses. Moreover, cell-to-cell contact between activated CD4 + T cells and blood-derived monocytes inhibits monocyte-derived IL-12 release, thereby leading to impaired T H 1 responses.…”

Photoactivational Cytokine‐modulatory Action of 8‐Methoxypsoralen plus Ultraviolet A in Lymphocytes, Monocytes, and Cutaneous T Cell Lymphoma Cells

“…To clarify these issues, we chose IL-8 as a representative cytokine to be tested, because it is the major and prototypic chemokine for neutrophils and T cells. 11 Normal PBMCs were untreated or treated with 8-MOP and/or UVA, and cultured for 72 h in the presence of lipopolysaccharide (LPS) or anti-CD3/CD28 mAbs. When cultured in the presence of LPS, which stimulates monocytes to produce IL-8, PBMCs treated with 8-MOP/UVA, but not 8-MOP or UVA alone, secreted a significantly higher amount of IL-8 than did untreated PBMCs.…”

“…These findings showed that 8-MOP/UVA augments IL-8 production by PBMCs, not only when monocytes are activated with LPS but also when T cells are stimulated via the T cell receptor/CD3 complex and costimulatory molecules. 11 With the use of immunomagnetic beads, PBMCs were deprived of CD4 + , CD8 + , or both CD4 + and CD8 + . They were treated with 8-MOP/UVA and cultured under stimulation with anti-CD3/CD28 mAbs.…”