Cytokine Profile of Bronchoalveolar Lavage–Derived CD4⁺, CD8⁺, and γδ T Cells in People with Asthma after Segmental Allergen Challenge

Abstract

T cell-derived cytokines play an important role in the pathogenesis of allergic asthma, but little is known about the cytokine profile of their different subsets. The aim of the present study was to investigate the cytokine production potential of CD4(+), CD8(+), or gammadelta(+) T cells derived from the bronchoalveolar space of mild atopic asthmatic subjects (n = 11) and nonatopic control subjects (n = 9) before and 24 h after segmental allergen challenge. The cytokine production was determined using the technique of intracellular cytokine detection by flow cytometry. Comparing asthmatic with control subjects we found no difference in the percentage of CD4(+), CD8(+), or gammadelta T cells in the bronchoalveolar lavage fluid before and after allergen challenge. Before allergen challenge the proportion of cells producing the cytokines interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-13 was not different in CD4(+) and CD8(+) cells. The major difference between the groups was an increased percentage of positive-staining cells for the T helper-(Th)2-cytokines IL-5 and IL-13 in the gammadelta T-cell subset. After allergen challenge, all T-cell subsets revealed a decreased proportion of cells producing the Th1-type cytokines IFN-gamma and IL-2. The percentage of IL-4- and IL-5-positive cells did not change in all subsets, and there was a decreased proportion of IL-13- positive cells in the CD4(+) subset. These findings indicate an increased Th2-cytokine profile in gammadelta T cells. After allergen challenge, the dysbalance between Th1 and Th2 cytokines was further accentuated by a reduction in Th1 cytokine-producing T cells.

Multiple Chemokine Receptors, Including CCR6 and CXCR3, Regulate Antigen-Induced T Cell Homing to the Human Asthmatic Airway

“…In addition to determining the percentage of Th2 cells present before and after segmental allergen challenge, we determined the percentage of Th1 cells present in the asthmatic airway because IFN-␥ may play an important role in either increasing or decreasing the severity of the asthmatic response (5,6). After stimulating cells with PMA and ionomycin, we observed that the percentage of IL-4-producing BAL T cells was similar before and after segmental allergen challenge, while the percentage of IFN-␥-producing BAL T cells was somewhat decreased following segmental allergen challenge, similar to a previous study (29,36). We also noted that in the absence of exogenous stimulation with PMA and ionomycin that the percentage of IL-4-producing BAL T cells was unchanged, but that the percentage of IFN-␥-producing cells was decreased significantly as compared with stimulated BAL T cells.…”

Human Vδ2 T cells are a major source of interleukin-9

“…Increased proportions of IL-5-and IL-13-producing γδ T cells are present in the bronchoalveolar lavage of patients with asthma (36). Accordingly, TGF-β, which is produced in response to allergen challenge (37), might drive the differentiation of local Vδ2 T cells into IL-9 producers.…”

The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo

“…Intracellular cytokine detection of BALF-derived T cells was performed as previously described (49). Briefly, BALF cells isolated from 11 patients were resuspended in RPMI 1640 supplemented with 10% fetal calf serum (Biochrom AG) (1 × 10 6 cells/ml).…”