T-helper type 2-dependent early recruitment of antigen non-specific CD4+ T cells in experimental asthma.

ABSTRACT

BACKGROUND: Following antigen challenge, adoptively transferred antigen-specific CD4(+) T cells induce allergic airway inflammation, comprised primarily of an increase in lymphocytes and eosinophils. OBJECTIVE: Our goal was to better understand the contribution of the GATA-3 transcription factor to the ability of adoptively transferred T cells to induce airway inflammation in the Brown Norway rat model of adoptively transferred asthma. METHODS: We transduced antigen-stimulated CD4+ T cells with recombinant retroviruses encoding enhanced green fluorescent protein (EGFP) only or EGFP and the GATA-3 transcription factor. Each population of transduced cells was adoptively transferred to naïve recipients that were then challenged with antigen. Airway inflammatory responses were then quantified. RESULTS: Our data indicate that T cells transduced with retroviruses encoding GATA-3 expressed high levels of GATA-3 protein as well as T-helper type 2 cytokines. Following adoptive transfer and airway antigen challenge, these gene-modified T cells induced robust inflammatory responses in the lungs and draining lymph nodes. Increased numbers of total inflammatory cells and eosinophils were recovered in the bronchoalveolar lavage fluid (BALF). In addition, the number of antigen non-specific CD4+ T cells recovered in the BALF as well as the lung and draining lymph nodes was enhanced in recipients of GATA-3 overexpressing T cells following antigen challenge. Nevertheless, the transduced CD4+ T cells comprised only a small percentage of the population of CD4+ T cells infiltrating the lung and were not detectable at all in the draining lymph nodes. CONCLUSION: These data provide evidence that GATA-3 plays a significant role in the ability of antigen-specific T cells to amplify allergic inflammatory responses in vivo by promoting the recruitment of endogenous antigen non-specific T cells to the lung.