Mechanisms of Allergy
The effects of CD8+γδ T cells on late allergic airway responses and airway inflammation in rats☆

https://doi.org/10.1016/S0091-6749(03)01720-2Get rights and content

Abstract

Background

Gamma-delta (γδ) T cells regulate immune responses to foreign protein at mucosal surfaces. Whether they can modify allergen-induced early (EAR) and late airway responses (LAR) is unknown.

Objective

We have tested the hypothesis that the CD8+ subtype of γδ T cells decreases allergen-induced LAR and airway eosinophilia in the rat.

Methods

Brown Norway rats were administered, intraperitoneally, 3.5 × 104 lymph node CD8+γδ T cells from naive or sensitized rats. The recipients were sensitized to ovalbumin (OVA) in Al(OH)3 3 days after cell transfer and challenged with aerosolized OVA 14 days later. Serum IgE was measured before allergen challenge. After challenge, lung resistance was monitored for 8 hours and then bronchoalveolar lavage (BAL) was analyzed for eosinophil major basic protein (MBP), IL-4, IL-5, IL-13, and IFN-γ messenger RNA–expressing cells.

Results

γδ T cells from naive donors significantly decreased LAR in OVA-challenged sensitized rats, whereas MBP+ eosinophils were decreased by both γδ T cells from naive and sensitized donors. EAR and serum IgE levels were unchanged. The expression of IL-4, IL-5, and IL-13 by BAL cells of γδ T cell recipients was attenuated compared with OVA-challenged controls. This was accompanied by an increase in the expression of IFN-γ.

Conclusions

Our results are consistent with a suppressive role of CD8+γδ T cells on allergic airway responses. However, only γδ T cells from naive donors inhibit LAR.

Section snippets

Animals and sensitization

BN rats (males; aged 10-12 weeks; 190-240 g) were purchased from Harlan Sprague Dawley UK (Blackthorn, UK) and were maintained in conventional animal facilities. Experimental procedures were approved by an institutional animal care committee. The animals were sensitized by a single subcutaneous injection of 20 μg OVA (grade V, Sigma, St Louis, Mo) in 1.0 mL normal saline containing 4.28 mg aluminum hydroxide gel (Anachemia Chemicals, Montreal, Canada). Simultaneously, 0.5 mL of Bordetella

CD8+γδ T-cell purification and transfer

The efficacy of immunomagnetic cell purification of CD8+γδ T cells harvested from the cervical lymph nodes was assessed by FACS analysis and demonstrated 88.8% ± 2.4% purity (n = 3). The survival ratios of CD8+γδ T cells (live cells/total cells) by Trypan blue exclusion, before their injection into the animals were 95.9% ± 2.2% (n = 3) and 95.8% ± 2.6% (n = 3) for cells harvested from naive and sensitized donors, respectively.

Cytokine expression by purified CD8+γδ T cells before transfer

Inhibitory immunomodulatory effects of γδ T cells have been

Discussion

In this study, we found that the administration of γδ T cells to rats before sensitization resulted in a marked inhibition of the LAR and of allergic inflammation evoked by aerosol challenge. The mechanism of the inhibition was not dependent on IgE; serum levels of OVA-specific IgE were unaffected by the γδ T cell transfers. T-cell cytokine profiles were biased toward a TH1 profile, consistent with the observed reduction in BAL fluid eosinophilia. Macrophages in the BAL fluid of recipients of

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    ☆

    Supported by Canadian Institutes for Health Research Grant 10381.

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