Background: T cells have been implicated in the pathogenesis of atopic asthma. We have previously shown that memory T helper cells (CD4+CD45RO+) are preferentially activated relative to naïve T helper cells (CD4+CD45RA+) after bronchial allergen challenge. However, specific T helper subpopulations that are activated in atopy and/or asthma remain undefined.
Objective: To determine the T helper subpopulations and activation phenotypes relevant to acute and stable asthma that may be common with or distinct from atopy.
Methods: Two groups of atopic asthmatics (ten acute and nine stable asthmatics) and two non-asthmatic groups (14 non-asthmatic atopics and eight normal non-atopic controls) were analysed. Ten acute asthmatics were assessed in the emergency room during an acute episode (FEV1 43.6% +/- 18.4). Nine stable asthmatics were assessed during a symptom-free period (FEV1 85% +/- 6). Using multiple colour flow cytometry we analysed T cell subpopulations and the expression of IL-2-receptor (IL-2R) and MHC-class II antigens (MHC II) on naïve and memory T helper cells in the peripheral blood of asthmatic and non-asthmatic groups.
Results: Atopic asthmatics (acute and stable) had an increased percentage of memory T helper cells expressing IL-2R compared with normal non-atopics (mean SD 16.1 +/- 6%, 12.4 +/- 2% and 7.7 +/- 1.8%, P < 0.05) but not compared with non-asthmatic atopics (10 +/- 3.5%). Naïve T helper cells had low expression of IL-2R and MHC II in all four groups. MHC II antigen expression was increased in memory T helper cells of asthmatics (acute and stable) compared with normal non-atopics (13.9 +/- 7.5, 10.6 +/- 5 and 4.9 +/- 2.5, P < 0.05) but not compared with non-asthmatic atopics (7.92 4). A novel finding was that IL-2R and the MHC II molecules were mainly expressed in non-overlapping populations and coexpression was found predominantly on memory T helper cells. Asthmatics (acute and stable) had higher proportion of double positive memory T helper cells (IL-2R+MHC II+) compared with both non-asthmatic groups (P < 0.05).
Conclusions: We demonstrate a differential expression of IL-2R+ and MCH II+ on CD45RO+ T helper cells that would suggest that there are three subsets of activated memory T helper cells in asthmatics. Two non-overlapping IL-2R+ or MHC II+ CD45RO+ T helper cells and a third subpopulation of activated cells that coexpress IL-2R and MHC II (double positives). This latter subpopulation is significantly higher in asthmatics (acute or stable) compared with both non-asthmatic groups, suggesting a specific T helper activation phenotype distinct to atopic asthmatics as compared with atopic non-asthmatics.