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-Tcell 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 T cell clones produced interleukin (IL)-2, IL-4, tumor necrosis factor-alpha and interferon-gamma (IFN-gamma) 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-gamma/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-gamma/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.

T-cell involvement in drug-induced acute generalized exanthematous pustulosis

“…Epstein-Barr virus-transformed (EBV-transformed) B-lymphoblastoid cell lines (B-LCLs) were generated as described (29) and cultured in RPMI-1640 supplemented with 10% FCS, 25 mM HEPES buffer, but without L-glutamine and without antibiotics.…”

HLA-restricted, processing- and metabolism-independent pathway of drug recognition by human alpha beta T lymphocytes.

“…The medium for culture of EBV-transformed B lymphoblastoid cell lines (B-LCL) was RPMI 1640 supplemented with 10% heat-inactivated FCS (Gibco, Paisley, UK), 25 mM Hepes buffer, but no L -glutamine and no antibiotics. B-LCL were generated as described (23).…”

Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates

“…Thus to determine whether the T M established by adoptive transfer could respond to antigen stimulation in vivo, we infused autologous T cells pulsed with CMV IE peptide (forming antigen-presenting T cells [T-APC]). We chose to use T-APCs because these cells could be easily prepared and prior human studies have shown that T cells expressing a foreign antigen can boost antigen-specific T M responses in vitro and in vivo (32,33). Peptide-pulsed T-APCs were lysed by the CMV-specific T cell clone in vitro ( Figure 8A) and were infused to macaque A99171 nine weeks after transfer of the CD19 + T CM -derived clone.…”