Infiltration of CD4+ CD8+ T cells, and expression of ICAM-1, Ia antigens, IL-1 alpha and TNF-alpha in the skin lesion of BALB/c mice undergoing repeated infestations with nymphal Ixodes ricinus ticks.

The skin cellular immune response of BALB/c mice was examined during three successive infestations with nymphal Ixodes ricinus ticks. An immunohistochemical analysis of skin cryostat sections 72 hr post-tick attachment revealed that CD4+ T cells outnumbered CD8+ T cells in all infestations. The CD4+:CD8+ T-cell ratio was 2.2:1 in the primary infestation, then increased to 3.2:1 and 4.7:1 in the secondary and tertiary infestations. No B lymphocytes (CD45R) were detected in the skin of control and infested mice. A positive staining of intercellular adhesion molecule-1 (ICAM-1) on vascular endothelial cells, dendritic cells and some other mononuclear cells was observed in the dermis. Also, a strong positive staining of Ia antigens on dendritic cells and infiltrated mononuclear cells was noted. The staining pattern was more intense and positive cells increased in number in the skin of re-infested mice compared to the primary infestation. In addition, cells such as epidermal keratinocytes, dermal dendritic cells and infiltrated mononuclear cells positive for the 'pro-inflammatory' cytokines interleukin-1 alpha (IL-1 alpha) and tumour necrosis factor-alpha (TNF-alpha) were localized in the skin of infested mice, as detected at the mRNA level by in situ hybridization and at protein level by immunostaining with antibodies. These results suggest that an antigen was presented to infiltrating T lymphocytes which then became activated. This event may explain the cutaneous delayed-type hypersensitivity previously described in tick-infected BALB/c mice. Importantly, this cutaneous reaction was not sufficient to protect the mouse against tick re-infestation. Furthermore, ICAM-1 could mediate, at least in part, the extravasation of inflammatory cells into the skin of infested mice.