Interferon-gamma inducible protein (IP-10) expression is mediated by CD8+ T cells and is regulated by CD4+ T cells during the elicitation of contact hypersensitivity.
To investigate the potential roles of CD4+ and CD8+ T cells during contact hypersensitivity, we examined the T-cell-dependent expression of proinflammatory cytokine genes in the responses to dinitrofluorobenzene and oxazolone. Whole cell RNA was isolated from challenged ear tissue and analyzed for level of cytokine gene expression by Northern blot and densitometry analysis. Expression of interleukin 1 beta and the three chemokine genes (IP-10, JE, and KC) examined was dependent on the hapten dose used for sensitization and correlated with the immune response, i.e., ear swelling, elicited. Antibody-mediated depletion of CD8+ T cells before sensitization resulted in the absence of IP-10 expression following hapten challenge, indicating the ability of immune CD8+ T cells to mediate IP-10 expression. Depletion of CD4+ T cells resulted in higher levels of IP-10 and KC expression during elicitation of contact sensitivity, suggesting CD4+ T cells inhibit the expression of these proinflammatory genes. Depletion of CD4+ T cells resulted in contact hypersensitivity responses of higher magnitude and depletion of CD8+ T cells resulted in responses of lower magnitude. Transfer of CD8+ T-cell-depleted immune cells resulted in low, but detectable levels of IP-10 expression, indicating the ability of some oxazolone-immune CD4+ T cells to mediate IP-10 expression. These results indicate the differential induction of proinflammatory cytokine gene expression during elicitation of contact hypersensitivity in which expression of IP-10 is primarily mediated by immune CD8+ T cells and inhibited by immune CD4+ T cells.
Abe
M
M
Department of Immunology, Cleveland Clinic Foundation, OH 44195-0001, USA.
Kondo
T
T
Xu
H
H
Fairchild
R L
RL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D017690:Cell Transplantation; D054357:Chemokine CXCL10; D018925:Chemokines / Q000235:genetics; D019743:Chemokines, CXC; D016207:Cytokines / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009994:Osmolar Concentration; D010081:Oxazolone / Q000276:immunology
D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D010081:Oxazolone; D004139:Dinitrofluorobenzene