Antigen‐presenting human T cells and antigen‐presenting B cells induce a similar cytokine profile in specific T cell clones

Abstract

One of the factors that may influence the cytokine secretion profile of a T cell is the antigen‐presenting cell (APC). Since activated human T cells have been described to express major histocompatibility complex (MHC) class II molecules as well as costimulatory molecules for T cell activation, like e.g. ICAM‐1, LFA‐3 and B7, they might play a role as APC and be involved in the regulation of T‐T cell interactions. To define further the role of T cells as APC we tested their capacity to induce proliferation and cytokine production in peptide‐ or allospecific T cell clones and compared it with conventional APC, like B lymphoblasts (B‐LCL) or HTLV‐1 ‐ transformed T cells, or with non‐classical APC, like activated keratinocytes or eosinophils. CD4⁺, DP‐restricted T cell clones specific for a tetanus toxin peptide (amino acids 947‐967) and CD4⁺, DR‐restricted allospecific Tcell clones produced interleukin (IL)‐2, IL‐4, tumor necrosis factor‐α and interferon‐γ (IFN‐γ) after phorbol 12‐myristate 13‐acetate and ionomycin stimulation and a more restricted cytokine pattern after antigen stimulation. Dose‐response curves revealed that the antigen‐presenting capacity of activated, MHC class II⁺, B7⁺ T cells was comparable to the one of B‐LCL. Both APC induced the same cytokine profile in the T cell clones despite a weaker proliferative response with T cells as APC. Suboptimal stimulations resulted in a lower IFN‐γ/IL‐4 ratio. Cytokine‐treated, MHC class II⁺ keratinocytes and eosinophils differed in the expression of adhesion molecules and their capacity to restimulate T cell clones. The strongly ICAM‐1‐positive keratinocytes induced rather high cytokine levels. In contrast, eosinophils, which express only low densities of MHC class II and no or only low levels of adhesion molecules (B7, ICAM‐1 and LFA3), provided a reduced signal resulting in a diminished IFN‐γ/IL‐4 ratio. We conclude that non‐classical APC differ in their capacity to restimulate T cell clones, whereby the intensity of MHC class II and adhesion molecules (B7, ICAM‐1) expressed seems to determine the efficacy of this presentation.