Allergy

Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths Ohnmacht, C. et al. Immunity 1 Sep 2010 (doi:10.1016/j.immuni.2010.08.011)

CD11c depletion severely disrupts Th2 induction and development in vivo Phythian-Adams, A. T. et al. J. Exp. Med. 6 Sep 2010 (doi:10.1084/jem.20100734)

Inflammatory dendritic cells — not basophils — are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen Hammad, H. et al. J. Exp. Med. 7 Sep 2010 (doi:10.1084/jem.20101563)

Basophils have recently attracted much interest as an antigen-presenting population, but the overall importance of basophils for T helper 2 (TH2)-type immunity has remained unclear. These new studies suggest that only dendritic cells (DCs) are crucial for the initiation of TH2-type immunity; basophils instead seem to be important for promoting chronic and secondary TH2-type responses. Ohnmacht et al. generated a transgenic mouse that constitutively lacked most basophils; these mice had normal TH2 cell responses to allergens and the helminth Nippostrongylus brasiliensis but showed resistance to IgE-dependent chronic allergic dermatitis and increased susceptibility to secondary helminth infections. However, DC-depleted mice had defective TH2 cell development following immunization, despite normal basophil recruitment. Similarly, Phythian-Adams et al. reported that although DC depletion inhibited TH2 cell development following infection with Schistosoma mansoni, depletion of basophils had no effect. Hammad et al. showed that only DCs were essential for TH2 cell responses to house dust mite allergen. High-affinity Fc receptor for IgE (FcεR1)+ inflammatory DCs, but not basophils, presented antigen and induced TH2 cell development following exposure to allergen. However, basophils did amplify the TH2-type response following allergen challenge. The description of a role for FcεR1+ DCs may explain why previous studies using FcεR1-specific antibodies to deplete basophils suggested that they were crucial for TH2 cell development.

T cell responses

Responses against a subdominant CD8+ T cell epitope protect against immunopathology caused by a dominant epitope Ruckwardt, T. J. et al. J. Immunol. 10 Sep 2010 (doi:10.4049/jimmunol.1001606)

The CD8+ T cell response to respiratory syncytial virus (RSV) in CB6F1 mice is focused on two viral epitopes — the immunodominant epitope H2-Kd–M282–90 and the subdominant epitope H2-Db–M187–195. Although RSV is cleared efficiently by the T cell response, this often results in immunopathology; this study looked at the contribution of these viral epitopes to immunity versus host damage. By mutating MHC-binding anchor residues in the RSV M2 and M proteins, the authors could study the responses to M282–90 and M187–195 separately. Absence of the dominant M282–90 epitope was compensated for by an increased response to the subdominant M187–195 epitope; this increased response effectively cleared RSV and resulted in less illness. Absence of M187–195 resulted in 'overcompensation' by the response to M282–90 and increased illness that correlated with decreased functionality of the dominant T cell population as measured by cytokine production. These results indicate that the subdominant H2-Db–M187–195 response exerts some form of beneficial control over the dominant H2-Kd–M282–90 response.