CYCLOSPORINE-A ABROGATES THE ACQUIRED-IMMUNITY TO CUTANEOUS REINFECTION WITH THE PARAPOXVIRUS ORF VIRUS

The effect of cyclosporin A (CsA) on host immunity to cutaneous reinfe ction with the parapoxvirus orf virus was studied in 6-month-old lambs . In control reinfected animals, clinical lesions and viral replicatio n (measured by the presence of vesicular/pustular lesions and viral an tigen) in regenerating epidermal cells were at a maximum on day 4 with resolution by day 9. Lesion histology revealed recruitment of T cells , B cells and dermal dendritic cells (DDC) which increased and decreas ed in parallel with the clinical course of the reinfection. In animals treated with CsA (25 mg/kg/day) 1 day before and for 8 days after rei nfection, more severe clinical lesions and viral replication typical o f primary infections were recorded and had not resolved by 28 days fol lowing reinfection. During CsA treatment, the recruitment of T cells, B cells and DDC was inhibited. With cessation of CsA treatment there w as dramatic recruitment of CD4(+) T cells followed by DDC then B cells to the lesion site but rapid onset of acquired immunity was not recor ded. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of cytokine mRNAs from lesion biopsies showed individual sheep variat ions. However, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) m RNAs were detected in the control reinfected animals on days 3 and/or 9 after reinfection but not on these days in animals undergoing treatm ent with CsA. In the untreated lambs there was an inexplicable lack of IL-2 and IFN-gamma mRNAs on day 6 after reinfection. Tumour necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) mRNAs were unaffected by CsA treatment. The data suggest that CsA abr ogates acquired immunity to orf virus reinfection by targetting T-cell lymphokine production.