CD4 T Cell Responses in Lung Tissue and Their Role in Th2 Protective Immunity

Abstract

The acquisition of protective immunity is a critical feature of the immune system. It is the unique ability of the adaptive immune response to generate and maintain long-lived antigen specific memory cells, which is the key to preventing reinfection and achieving the goal of protective immunity. The importance of secondary lymphoid tissue (such as lymph nodes) as a site of effector CD4 T cell responses and the generation, dissemination and maintenance of memory CD4 T cells is well accepted. However, a key research area needing investigation is the basic biology of the CD4 T cell, particularly the recirculation, distribution and maintenance of CD4 T cells at sites throughout the body. To address these issues we used Nippostrongylus brasiliensis as a model of CD4 mediated protective immunity, combined with G4/IL-4 reporter mice. We show that the lung environment is critical for the priming of CD4 T cells and conferring protective immunity. In contrast to others we find no protective role for the CD4 T cell population of the skin and only a minor role for the population within the gut. In a separate study we used the drug fingolimod (FTY720) to block the cellular trafficking between lymph node and lung tissue during immune responses. Interestingly, our findings show that protection against N. brasiliensis infection is maintained when CD4 T cell recirculation between the lung and lymph node is blocked. Furthermore, we reveal that peripheral lung residing CD4 T cells are sufficient for conferring protective immunity in the N. brasiliensis model, generating support for the model of effector lymphoid tissue. When N. brasiliensis experienced CD4 T cells were localised to the lung by intranasal adoptive transfer they were able to confer protection against infection in otherwise naive animals, as early as 48 hours post infection. The most striking finding of this work is the discovery that memory CD4 T cells residing in the lung that are sufficient to confer protection against reinfection. Identifying the factors in the lung and lymph node that induce and support this CD4 T cell subset will be an important area of future research given its high relevance to the design of vaccines against parasite infections.