Atopic asthma: differential activation phenotypes among memory T helper cells

Background T cells have been implicated in the pathogenesis of atopic asthm a. We have previously shown that memory T helper cells (CD4(+)CD45RO(+)) ar e preferentially activated relative to naive T helper cells (CD4(+)CD45RA()) after bronchial allergen challenge. However, specific T helper subpopula tions that are activated in atopy and/or asthma remain undefined. Objective To determine the T helper subpopulations and activation phenotype s relevant to acute and stable asthma that may be common with or distinct f rom atopy. Methods Two groups of atopic asthmatics (ten acute and nine stable asthmati cs) 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 stab le 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 III) on naive and memory T helper cells in the peripheral blood of asthmatic an d 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 (m ean SD 16.1 +/- 6%, 12.4 +/- 2% and 7.7 +/- 1.8%, P < 0.05) but not compare d with non-asthmatic atopics (10 <plus/minus> 3.5%). Naive T helper cells h ad low expression of IL-2R and MHC II in all four groups. MHC If antigen ex pression was increased in memory T helper cells of asthmatics (acute and st able) 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 no vel finding was that IL-2R and the MHC II molecules were mainly expressed i n nonoverlapping populations and coexpression was found predominantly on me mory 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 subse ts 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 act ivated cells that coexpress IL-2R and MHC II (double positives). This latte r subpopulation is significantly higher in asthmatics (acute or stable) com pared with both non-asthmatic groups, suggesting a specific T helper activa tion phenotype distinct to atopic. asthmatics as compared with atopic non-a sthmatics.