Interleukin‐4 and interleukin‐5 are rarely co‐expressed by human T cells

Abstract

Interleukin (IL)-4 and IL-5 are two cytokines which synergize in the induction of several biological effector functions. They are produced by mouse and human T helper 2 (Th2) and T helper 0 (Th0) cells. Little is known about the regulation of the two cytokines at the single-cell level. Here we show, using a flow cytometric intracellular staining technique, that IL-4 and IL-5 are predominantly produced by different human peripheral CD4+ and CD8+ T cells, whereas interferon (IFN)-gamma and IL-2 are produced by the same cells. In contrast, cloned human Th0 and Th2 cells were able to produce IL-4 and IL-5 simultaneously. The segregation of IL-4 and IL-5 in activated peripheral T cells was found within 72 h of activation upon anti-CD3 or phorbol ester + ionomycin stimulation. The kinetics of IL-4 and IL-5 production were different at the mRNA and the intra- and extracellular protein level, indicating that the cytokines are regulated differently. T cells from three patients with hyper-IgE syndrome did not display a substantial proportion of IL-4/IL-5 double-positive cells. However, simultaneous production could be induced in normal human T cells after prolonged stimulation with a minimum of two restimulation cycles. We conclude that the simultaneous production of IL-4 and IL-5 is a feature of repetitively activated human T cells.

Revisiting Tolerance Induced by Autoantigen in Incomplete Freund’s Adjuvant

“…These data are consistent with the newly emerging view that type 1 and type 2 responses are not mediated by classic Th1 or Th2 cells that coexpress the different type 1 or type 2 cytokines in predefined sets (61). Instead, the data suggest that the production of each cytokine within the type 1 or type 2 response is independently regulated, as has been first noted with in vitro polarized TCR-transgenic cells (62), and mitogen-stimulated cells (63)(64)(65). The data are also consistent with the finding that differentiation of IL-4-producing memory cells depends on the presence of IL-4/13, but that of IL-5-producing memory cells is independent of these cytokines (66).…”

Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones

“…accumulating data indicating that IL-2 production is not restricted to the Th1 subset in humans [9,24,25], we found that the synthesis of IL-2 by the TCC did not completely match the conventional Th1-Th2 classification. Similarly, IL-5 production was not significantly higher among Th2 clones, and this appeared to reflect the ability of some cells to synthesize exclusively either IL-4 or IL-5, as has been described in previous studies [26].…”

Direct Visualization of Cytokine-Producing Recall Antigen-Specific CD4 Memory T Cells in Healthy Individuals and HIV Patients

“…Based on studies of long-term cultured T cell clones (which can lose differentiation in cell culture) and on assays that are not suited to defining the cellular sources of the individual cytokine, it has been widely held that the clear-cut polarization of T cell responses along the Th1/Th2 paradigm seen in the mouse does not hold for humans (26). Our data, obtained at single cell resolution, suggest that IFN-␥ and IL-5 can be expressed by human memory T cells in a mutually exclusive manner, favoring emerging concepts that the expression of type 1 and type 2 cytokine genes is individually regulated in T cells (27)(28)(29). Indeed, when we performed two-color ELISPOT assays simultaneously detecting IL-5 and IFN-␥, we found that these cytokines were not produced by Th0-type cells that coexpress both, but that IFN-␥ and IL-5 were produced by different CD4 cells (manuscript in preparation).…”