title: Common clonal origin of central and resident memory T cells following skin immunization.
abstract: Central memory T (TCM) cells in lymph nodes (LNs) and resident memory T (TRM) cells in peripheral tissues have distinct roles in protective immunity. Both are generated after primary infections, but their clonal origins have been unclear. To address this question, we immunized mice through the skin with a protein antigen, a chemical hapten, or a non-replicating poxvirus. We then analyzed antigen-activated T cells from different tissues using high-throughput sequencing (HTS) of the gene encoding the T cell receptor (TCR) β-chain (Trb, also known as Tcrb) using CDR3 sequences to simultaneously track thousands of unique T cells. For every abundant TRM cell clone generated in the skin, an abundant TCM cell clone bearing the identical TCR was present in the LNs. Thus, antigen-reactive skin TRM and LN TCM cell clones were derived from a common naive T cell precursor after skin immunization, generating overlapping TCR repertoires. Although they bore the same TCR, TRM cells mediated rapid contact hypersensitivity responses, whereas TCM cells mediated delayed and attenuated responses. Studies in human subjects confirmed the generation of skin TRM cells in allergic contact dermatitis. Thus, immunization through skin simultaneously generates skin TRM and LN TCM cells in similar numbers from the same naive T cells.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gaide
authors.affiliation: Adaptive Biotech, Seattle, Washington, USA.
authors.forename: Ryan O
authors.initials: RO
authors.lastname: Emerson
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Nizza
authors.affiliation: Adaptive Biotech, Seattle, Washington, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Desmarais
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Harlan
authors.initials: H
authors.lastname: Robins
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Clark
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011212:Poxviridae / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D006241:Haptens; D016693:Receptors, Antigen, T-Cell, alpha-beta