Tbet Deficiency Causes T Helper Cell Dependent Airways Eosinophilia and Mucus Hypersecretion in Response to Rhinovirus Infection

Current understanding of adaptive immune,particularly t cell,responses to human rhinoviruses (rv) is limited. memory t cells are thought to be of a primarily t helper 1 type,but both t helper 1 and t helper 2 memory cells have been described,and heightened t helper 2/ lessened t helper 1 responses have been associated with increased rv-induced asthma exacerbation severity. we examined the contribution of t helper 1 cells to rv-induced airways inflammation using mice deficient in the transcription factor t-box expressed in t cells (tbet),a critical controller of t helper 1 cell differentiation. using flow cytometry we showed that tbet deficient mice lacked the t helper 1 response of wild type mice and instead developed mixed t helper 2/t helper 17 responses to rv infection,evidenced by increased numbers of gata binding protein 3 (gata-3) and rar-related orphan receptor gamma t (rorγt),and interleukin-13 and interleukin-17a expressing cd4+ t cells in the lung. forkhead box p3 (foxp3) and interleukin-10 expressing t cell numbers were unaffected. tbet deficient mice also displayed deficiencies in lung natural killer,natural killer t cell and γδt cell responses,and serum neutralising antibody responses. tbet deficient mice exhibited pronounced airways eosinophilia and mucus production in response to rv infection that,by utilising a cd4+ cell depleting antibody,were found to be t helper cell dependent. rv induction of t helper 2 and t helper 17 responses may therefore have an important role in directly driving features of allergic airways disease such as eosinophilia and mucus hypersecretion during asthma exacerbations. © 2016 glanville et al.