TY - JOUR
T1 - Virus-Specific CD4+ Memory-Phenotype T Cells Are Abundant in Unexposed Adults
AU - Su, Laura F.
AU - Kidd, Brian A.
AU - Han, Arnold
AU - Kotzin, Jonathan J.
AU - Davis, Mark M.
N1 - Funding Information:
We thank Kai Wucherpfennig for providing the HLA-DR4 stable transfectant cell line for the production of HLA-DR monomers. Thanks also go to Yueh-hsiu Chien, John Imboden, Jonathan Graf, Elizabeth Mellins, Peter Ebert, Marc Jenkins, and Wong Yu for helpful discussions. We thank Bithi Chatterjee for helpful advice on deriving dendritic cells, Andrew Prentice for helpful suggestions, and Cristina Tato for manuscript edits. L.F.S was supported by a Daland fellowship from the American Philosophical Foundation and an ACR REF Rheumatology Scientist Development Award and is currently supported by a K08 award from National Institutes of Health (NIH) grant K08 AR059760. A.H. is supported by NIH training grant 5 T32 DK007056-36. Other research support came from grants from the NIH (U19 AI057229 and U19AI090019) and the Howard Hughes Medical Institute to M.M.D. L.F.S. and M.M.D. were responsible for design of the research. L.F.S performed experiments and analyzed data. A.H. designed the TCR sequencing primers and protocol. B.A.K. provided statistical expertise and analyzed gene expression data. J.J.K. assisted with HA epitope identification and performed the HAI assays. L.F.S wrote the paper. M.M.D, A.H., B.A.K, and J.J.K edited the manuscript.
PY - 2013/2/21
Y1 - 2013/2/21
N2 - Although T cell memory is generally thought to require direct antigen exposure, we found an abundance of memory-phenotype cells (20%-90%, averaging over 50%) of CD4+ T cells specific to viral antigens in adults who had never been infected. These cells express the appropriate memory markers and genes, rapidly produce cytokines, and have clonally expanded. In contrast, the same T cell receptor (TCR) specificities in newborns are almost entirely naïve, which might explain the vulnerability of young children to infections. One mechanism for this phenomenon is TCR cross-reactivity to environmental antigens, and in support of this, we found extensive cross-recognition by HIV-1 and influenza-reactive T lymphocytes to other microbial peptides and expansion of one of these after influenza vaccination. Thus, the presence of these memory-phenotype T cells has significant implications for immunity to novel pathogens, child and adult health, and the influence of pathogen-rich versus hygienic environments.
AB - Although T cell memory is generally thought to require direct antigen exposure, we found an abundance of memory-phenotype cells (20%-90%, averaging over 50%) of CD4+ T cells specific to viral antigens in adults who had never been infected. These cells express the appropriate memory markers and genes, rapidly produce cytokines, and have clonally expanded. In contrast, the same T cell receptor (TCR) specificities in newborns are almost entirely naïve, which might explain the vulnerability of young children to infections. One mechanism for this phenomenon is TCR cross-reactivity to environmental antigens, and in support of this, we found extensive cross-recognition by HIV-1 and influenza-reactive T lymphocytes to other microbial peptides and expansion of one of these after influenza vaccination. Thus, the presence of these memory-phenotype T cells has significant implications for immunity to novel pathogens, child and adult health, and the influence of pathogen-rich versus hygienic environments.
UR - http://www.scopus.com/inward/record.url?scp=84874253445&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.10.021
DO - 10.1016/j.immuni.2012.10.021
M3 - Article
C2 - 23395677
AN - SCOPUS:84874253445
SN - 1074-7613
VL - 38
SP - 373
EP - 383
JO - Immunity
JF - Immunity
IS - 2
ER -