Proinflammatory Roles of T-Cell Receptor (TCR) γδ and TCR αβ Lymphocytes in a Murine Model of Asthma

Abstract

The role of lymphocytes bearing alphabeta or gammadelta T-cell receptors (TCRs) was assessed during the acute allergic response in a mouse model of asthma. The inflammatory immune response to ovalbumin (OVA) was characterized in wild-type C57BL/6J mice and congenic TCRbeta(-/-) and TCRdelta(-/-) mice by evaluation of airway eosinophilia, histopathology, serum immunoglobulin (Ig)E levels, and in vivo airway responsiveness to methacholine. OVA-challenged wild-type mice demonstrated marked pulmonary inflammation, evidenced by airway eosinophilia (68 +/- 7 x 10(4) cells), peribronchial lympho-plasmocytic infiltration, and elevated serum IgE (4.9 +/- 0.6 microg/ml). These responses were markedly attenuated in TCRdelta(-/-) animals (5.0 +/- 1.0 x 10(4) eosinophils and 1.6 +/- 0. 3 microg/ml IgE) and were completely absent in TCRbeta(-/-) mice (< 1 x 10(3) eosinophils and 0.38 +/- 0.21 microg/ml IgE). Similar results were observed in mice treated with anti-TCRgammadelta or anti-TCRalphabeta monoclonal antibodies. Airway responsiveness to aerosolized methacholine was also reduced in challenged TCRdelta(-/-) animals relative to challenged wild-type mice. These results demonstrate that acute allergic airway responses are dependent upon intact TCRalphabeta and TCRgammadelta lymphocyte function and that TCRgammadelta cells promote acute airway sensitization.

Chronic Inhaled Ovalbumin Exposure Induces Antigen-Dependent but Not Antigen-Specific Inhalational Tolerance in a Murine Model of Allergic Airway Disease

“…Rather, the depletion of TCR␥␦ cells had an inhibitory effect in our discontinuous model, similar to its effect in the acute stages of allergic airway inflammation. 14,20 The maintenance of elevated serum IgE levels in the absence of airway inflammatory responses in continuous mice suggested that our inhalational tolerance was because of local mechanisms rather than systemic lymphocyte clonal deletion or anergy. If chronic OVA aerosol exposure had induced tolerance via clonal deletion or development of a dominant, antigen-specific, inhibitory T-cell population, tolerance should have been sustained with the absence of antigen or recalled with re-exposure.…”

“…at days Ϫ3 and 3 of the final 10-day aerosol exposure. 14 The OVA aerosols were generated by a Lovelace nebulizer (In-Tox Products, Albuquerque, NM) into a 7.6-L inhalation exposure chamber to which mice placed in plastic restraint tubes (Research and Consulting Co., AG, Basel, Switzerland) were attached. Chamber airflow was 10 L/minute.…”

“…In addition, local inhalational tolerance could not be broken by the intraperitoneal administration of anti-TCR␥␦ antibodies before the final week of OVA aerosols in continuous mice (data not shown), even though it markedly reduced the airway eosinophilia in discontinuous mice in a similar degree to its effect in acute animals. 14 …”

CCL25 induces α4β7 integrin‐dependent migration of IL‐17+γδ T lymphocytes during an allergic reaction

“…γδ T cells have been shown to migrate into the airways during allergic inflammation highly controlled by a chemotactic gradient of chemokines produced in tissue [5,[7][8][9][10][11]. We have previously demonstrated that allergen-induced γδ T-cell accumulation is * These authors contributed equally to this work.…”

“…This unique subset of lymphocytes can provide rapid tissue-specific immune responses, without the requirement of antiCorrespondence: Dr. Carmen Penido e-mail: cpenido@far.fiocruz.br gen presentation or clonal expansion, and is able to produce a large repertory of Th1-, Th2-, and Th17-associated cytokines [2][3][4][5][6]. These characteristics make γδ T cells a crucial first line of defense during infection, tissue damage, or stress.γδ T cells have been shown to migrate into the airways during allergic inflammation highly controlled by a chemotactic gradient of chemokines produced in tissue [5,[7][8][9][10][11]. We have previously demonstrated that allergen-induced γδ T-cell accumulation is * These authors contributed equally to this work.…”