UMMS Affiliation

Department of Pathology

Publication Date


Document Type



Immunology of Infectious Disease | Immunopathology | Microbiology | Pathology | Respiratory Tract Diseases | Virus Diseases | Viruses


Although much is known about the mechanisms by which pathogen recognition drives the initiation of T cell responses, including those to respiratory viruses, the role of pathogen recognition in fate decisions of T cells once they have become effectors remains poorly defined. Here, we review our recent studies that suggest that the generation of CD4 T cell memory is determined by recognition of virus at an effector "checkpoint." We propose this is also true of more highly differentiated tissue-restricted effector cells, including cytotoxic "ThCTL" in the site of infection and TFH in secondary lymphoid organs. We point out that ThCTL are key contributors to direct viral clearance and TFH to effective Ab response, suggesting that the most protective immunity to influenza, and by analogy to other respiratory viruses, requires prolonged exposure to antigen and to infection-associated signals. We point out that many vaccines used today do not provide such prolonged signals and suggest this contributes to their limited effectiveness. We also discuss how aging impacts effective CD4 T cell responses and how new insights about the response of aged naive CD4 T cells and B cells might hold implications for effective vaccine design for both the young and aged against respiratory viruses.


CD4 T cells, TFH, ThCTL, immune memory, influenza, pathogen recognition, virus

Rights and Permissions

Copyright: © 2018 Devarajan, Jones, Kugler-Umana, Vong, Xia and Swain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version



Front Immunol. 2018 Mar 26;9:596. doi: 10.3389/fimmu.2018.00596. eCollection 2018. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in immunology

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.