INFILTRATION OF CD4-CELLS, AND EXPRESSION OF ICAM-1, IA ANTIGENS, IL-1-ALPHA AND TNF-ALPHA IN THE SKIN LESION OF BALB( CD8+ T)C MICE UNDERGOING REPEATED INFESTATIONS WITH NYMPHAL IXODES-RICINUS TICKS/

The skin cellular immune response of BALB/c mice was examined during t hree successive infestations with nymphal Ixodes ricinus ticks. An imm unohistochemical analysis of skin cryostat sections 72 hr post-tick at tachment revealed that CD4(+) T cells outnumbered CD8(-) T cells in al l infestations. The CD4(+):CD8(+) T-cell ratio was 2.2:1 in the primar y 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 s kin 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. Al so, a strong positive staining of Ia antigens on dendritic cells and i nfiltrated mononuclear cells was noted. The staining pattern was more intense and positive cells increased in number in the skin of re-infes ted mice compared to the primary infestation. In addition, cells such as epidermal keratinocytes, dermal dendritic cells and infiltrated mon onuclear cells positive for the 'pro-inflammatory' cytokines interleuk in-1 alpha (IL-1 alpha) and tumour necrosis factor-alpha (TNF-alpha) w ere localized in the skin of infested mice, as detected at the mRNA le vel by in situ hybridization and at protein level by immunostaining wi th 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 descri bed in tick-infested 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.