We aimed to investigate the role of CD4+ cells in the bronchial late phase response (LPR) in a mouse-model of asthma, characterized by an allergen-specific LPR.

Male Balb/C mice (6–8 weeks) were sensitized by ovalbumin (OVA) (i.p.) on alternate days from d1 till d13. The challenge phase comprised daily nebulizations of OVA from d33 till d40. On d47 500ul PBS (control) or 100 μg GK1.5 (depleting anti-CD4 monoclonal antibody) was administered i.p. The LPR was induced by nebulized OVA on d50. The enhanced pause (PenH) was measured every 30 seconds during 6 hours by body plethysmography. The mice were sacrificed for flowcytometric analysis of whole blood, differential cell counts and cytokine measurements on broncho-alveolar lavage (BAL), and for RT-PCR on lung tissue.

Within the CD3+ population, GK1.5 diminished the CD4+ cells by more than 90%. In the control mice an LPR could be induced with PenH peaking at 240 min whereas in the GK1.5 group the LPR was inhibited. The area under the curve of the PenH/time curve was lower in the GK1.5 mice compared to the control mice (p=0.03, t-test). BAL lymphocyte, monocyte and eosinophil counts were lower in the GK1.5 group (p=0.03, p=0.03 and p=0.02 respectively, t-test). BAL IFN-γ was lower in the GK1.5 group (p=0.02, t-test). IL-4, IL-5 and IFN-γ-mRNA tended to be decreased in the GK1.5 group.

Blocking/depleting of CD4+ cells inhibits the LPR in a mouse model of asthma. Thus, CD4+ lymphocytes might play a key role in the induction of the bronchial LPR.