TY - JOUR
T1 - Nickel-specific CD4+ and CD8+ T cells display distinct migratory responses to chemokines produced during allergic contact dermatitis
AU - Sebastiani, Silvia
AU - Albanesi, Cristina
AU - Nasorri, Francesca
AU - Girolomoni, Giampiero
AU - Cavani, Andrea
PY - 2002
Y1 - 2002
N2 - 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-1β, 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.
AB - 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-1β, 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.
KW - Allergic contact dermatitis
KW - Chemokines
KW - Leukocyte trafficking
KW - Skin
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U2 - 10.1046/j.1523-1747.2002.01771.x
DO - 10.1046/j.1523-1747.2002.01771.x
M3 - Article
C2 - 12060402
AN - SCOPUS:0036072232
VL - 118
SP - 1052
EP - 1058
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 6
ER -