My ongoing and future research endeavors are centered on two lines of research, both of which strive to gain further insights into how CD4 T cells function to protect against influenza A virus (IAV).
The first is focused on understanding the cellular and molecular mechanisms by which memory CD4 T cells enhance early innate inflammatory cytokines and chemokines that correlate with early control of IAV. Such knowledge has broad translational impact as it could also provide insight into how CD4 T cells promote immune mediated inflammatory autoimmune diseases.
The second research avenue is centered on the hypothesis that memory CD4 T cells, in addition to orchestrating and participating in more rapid and effective anti-viral recall responses, orchestrate accelerated healing in infected or damaged tissue through enhanced activation and mobilization of innate cells involved in tissue repair processes. The beneficial role of memory CD4 T cells in promoting tissue repair has not previously been appreciated and has broad translational application.
The ultimate goal of research in my lab is to gain insight into how immune cells participate in vaccine induced protection. Understanding how immune cells function to mediate protection is key to the development of novel and innovative vaccination strategies against pathogens, such as IAV, for which vaccines that induce long-lived universal protection have yet to be formulated. Research leading to the development of novel strategies to protect individuals from potential pandemic or circulating strains of influenza that differ from the predicted vaccine strain is of paramount importance as influenza remains a serious public health concern.
- Swain, S. L., Strutt, T.M., and K.K. McKinstry. 2015. “Immunity to Viral Infection: CD4 T Cell Immunity to Viral Infection”. In Biron (Ed) Encyclopedia of Immunobiology. Oxford: Elsevier (In Press).
- Torrado, E., Fountain, J., Tighe, M., Reiley, W., Pearl, J.E., Zak, D.E., Thompson, E.G., Aderem, A., Solache, A., McKinstry, K., Strutt, T., Swain, S., and A.M. 2015. Cooper. Interleukin 27 regulates CD4 T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis Journal of Experimental Medicine 212:1449-63.
- McKinstry, K.K.*, Strutt, T.M.*, Bautista, B. Zhang, W., Kuang, Y., Cooper, A.M., and S.L. Swain. 2014. Effector CD4 T cell transition to memory requires late cognate interactions that induce autocrine IL-2. Nature Communications 5:5377 doi: 10.1038/ncomms6377. *Authors contributed equally.
- Stewart S., Guest, I., McKinstry, K.K., Strutt, T.M., Kohlmeier, J.E., Brincks, E., Tighe, M., Blackman, M.A., Woodland, D.L., Dutton, R.W., and S.L. Swain. Intraepithelial T-cell cytotoxicity, induced bronchus associated lymphoid tissue, and proliferation of pneumocytes in experimental mouse models of influenza. Viral Immunology. 27:484-96.
- McKinstry K.K., and Strutt T.M. 2014. “Regulation and Maintenance of Adaptive Immunity”. In L.M. McManus, R.N. Mitchell (Eds.) Pathobiology of Human Disease. San Diego: Elsevier; p.20-35.
- Strutt, T.M., McKinstry, K.K., Marshall, N.B., Vong, A.M., Dutton, R.W., and S.L. Swain. 2013. Multipronged CD4 T cell effector and memory responses cooperate to provide potent immunity against respiratory virus. Immunological Reviews 255:149-64.
- McKinstry, K.K., Dutton, R.W., Swain, S.L., and M. Strutt. 2013. Memory CD4 T cell-mediated immunity against influenza A virus: more than a little helpful. Archivum Immunologiae et Therapiae Experimentalis 61:341-53.
- Hamada, H., Bassity, E., Flies, A., Strutt, T.M., Garcia-Hernandez, M-L., McKinstry, K.K., Zou, T., Swain, S.L., and R.W. Dutton. 2013. Multiple effector mechanisms of CD8+ T cells protect against influenza infection. Journal of Immunology 190:296-306.
- Strutt, T.M., McKinstry, K.K., Kuang, Y., Bradley, L.M., and S.L. Swain. 2012. Memory CD4+ T cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors. Proceedings from the National Academy of Sciences 109:E2551-60.
- Pearl, J.E., Torrado, E., Tighe, M., Fountain, J.J., Solache, A., Strutt, T., Swain, S., Appelberg, R., and A. Cooper. 2012. Nitric oxide inhibits accumulation of CD4+CD44hiTbet+CD69lo T cells in mycobacterial infection. European Journal of Immunology 42: 3267-79.
- McKinstry, K.K.*, Strutt, T.M.*, Kuang, Y., Brown, D.M., Sell, S., Dutton, R.W., and S.L. Swain. 2012. Memory CD4+ T-cells protect against influenza by multiple synergizing mechanisms. Journal of Clinical Investigation 122: 2847-2856. *Authors contributed equally.
- Swain, S.L., McKinstry, K.K., and M. Strutt. 2012. Expanding roles for CD4+ T cells in immunity to viruses. Nature Reviews Immunology 12:136-148.
- Strutt, T.M., McKinstry, K.K., and S.L. Swain. “Crossroads between innate and adaptive immunity III: Control of innate immunity by memory CD4+ T cells”. In B. Pulendran, P.D. Katsikis, and S.P. Schoenberger (Eds.) Advances in Experimental Medicine and Biology Vol.780: 57-68.
- McKinstry K.K., Strutt T.M., and S.L. Swain. 2011. Hallmarks of CD4+ T cell immunity against influenza. The Journal of Internal Medicine 269:507-18.
- Strutt, T.M., McKinstry, K.K., Dibble, J.P., Winchell, C., Kuang, Y., Curtis, J.D., Huston, G., Dutton, R.W., and S.L. Swain. 2010. Memory CD4+ T cells induce innate responses independent of pathogen. Nature Medicine 16: 558-564.
- McKinstry, K.K., Strutt, T.M.,L. Swain. 2010. The potential of CD4+ T cell memory. Immunology 130:1-9.
- McKinstry, K.K., Strutt, T.M.,L. Swain. 2010. Regulation of CD4+ T cell contraction during pathogen challenge. Immunological Reviews 236: 110-124.
- McKinstry, K.K.*, Strutt, T.M.*, Buck, A., Curtis, J., Dibble, J., Huston, G., Hamada, H., Dutton, R.W., Sell, S., and S.L. Swain. 2009. IL-10 deficiency unleashes an influenza specific TH-17 response and enhances survival against high dose challenge. Journal of Immunology 182:7353-63. *Authors contributed equally.
- Hamada, H., Garcia-Hernandez, M-L., Reome, J., Misra, S.K., Strutt, T.M., McKinstry, K.K., Cooper, A.M., Swain, S.L., and R.W. Dutton. 2009. Tc17, a unique subset of CD8+ T cells that can protect against lethal influenza challenge. Journal of Immunology 182: 3469-81.
- Strutt, T.M., McKinstry, K.K., and S.L. Swain. 2009. Functionally diverse subsets in CD4+ T cell responses against influenza. Journal of Clinical Immunology 29:145-50.
- Jelly-Gibbs, D. M., Strutt, T.M., McKinstry, K.K., and S.L. Swain. 2008. Influencing the fates of CD4+ T cells on the path to memory: lessons from influenza. Immunology and Cell Biology 86:343-52.
- K.K., Strutt, T.M., and S.L. Swain. 2008. The effector to memory transition of CD4+ T cells. Immunologic Research 40:114-27.
- Jelly-Gibbs, D.M., Dibble, J.P., Brown, D.M., Strutt, T.M., McKinstry, K.K., and S.L. Swain. 2007. Persistent depots of influenza antigen fail to induce a cytotoxic CD8+ T cell response. Journal of Immunology 178:7563-70.
- Powell, T.J.*, Strutt, T.*, Reome, J., Hollenbaugh, J.A., Roberts, A.D., Woodland, D.L., Swain, S.L., Dutton, R. W. 2007. Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus. Journal of Immunology 178:1030-8. *Authors contributed equally.
- Swain, S.L., Agrewala, J.N., Brown, D.M., Jelley-Gibbs, D.M., Golech, S., Huston, G., Jones, S.C, Kamperschroer, C., Lee, W-H., McKinstry, K.K., Roman, E., Strutt, T. and N. Weng. 2006. CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza. Immunological Reviews 211:8-22.
- Strutt, T.M., Uzonna, J., McKinstry, K.K, and P. Bretscher. 2006. Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC. International Immunology 18:719-28.
- McKinstry, K., Ismail, N., Peters, N., Strutt, T.M., and P. Bretscher. 2005. Non-interference, independence and coherence of immune responses: Implications for macro immunology and strategies of intervention. In R.M. Gorczynski (Ed) Altered Immunoregulation and Human Disease. Kerala: Research Signpost; p. 93-113.
- Strutt, T. and P. Bretscher. 2005. Cooperation between CD4+ T helper cells is required for the generation of alloantigen-specific, IFN-g-producing human CD4+ T cells. Immunology and Cell Biology 83:175-81.