title: Nickel-specific CD4(+) and CD8(+) T cells display distinct migratory responses to chemokines produced during allergic contact dermatitis.
abstract: Development of allergic contact dermatitis to haptens depends upon a balance between CD8(+) T lymphocytes with pathogenic activity and CD4(+) T cells, which comprise both effector and regulatory cells. Thus, differential recruitment of CD8(+) and CD4(+) lymphocytes to sites of hapten challenge may have considerable impact on disease expression. Here the migration of cutaneous lymphocyte-associated antigen+, nickel-specific CD8(+) and CD4(+) T cell lines were compared with a panel of chemokines produced in the skin during allergic contact dermatitis. CCL17/TARC and CCL22/MDC induced a 3-fold higher migration of CD4(+) compared with CD8(+) lymphocytes. In contrast, CXCL10/IP-10 was 2-fold more potent in attracting CD8(+) cells. These findings were consistent with the higher expression of CCR4 and CXCR3 on CD4(+) and CD8(+) T cell lines, respectively. Moreover, CCR4 expression was high on nickel-specific T helper 2, intermediate on T helper 1 and T cytotoxic 2, and almost undetectable on T cytotoxic 1 clones. On the contrary, CXCR3 was expressed by T cytotoxic 1 and 2 and T helper 1, but not T helper 2 clones. Reverse transcription-polymerase chain reaction analysis of the skin before and after hapten challenge revealed the constitutive presence of TARC, and the early appearance of CCL2/MCP-1, followed by IP-10, CCL4/MIP-1beta, and MDC mRNA. Supernatants from activated keratinocytes induced a strong migration of CD8(+) lymphocytes, which was blocked by neutralization of IP-10. Conversely, supernatants from immature and mature dendritic cells attracted mostly CD4(+) lymphocytes in a TARC- and MDC-dependent manner. Our data indicate that distinct chemokines and cell types control the accumulation of CD8(+) and CD4(+) T cells within inflamed skin.
authors.affiliation: Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sebastiani
authors.forename: Cristina
authors.initials: C
authors.lastname: Albanesi
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D009532:Nickel / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000096:biosynthesis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D018925:Chemokines; D012333:RNA, Messenger; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D009532:Nickel