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The rabbit model for HTLV-I infection
Abstract
Rabbit HTLV-I transformed cell lines possessing diverse biological properties were derived in vitro from peripheral blood lymphocytes of New Zealand White rabbits. Two of the cell lines caused fatal leukemia with infiltration in the lungs, spleen, liver and kidneys of adult rabbit recipients within 10 days of inoculation. To determine whether cell lineage influences pathogenesis, the fatal leukemogenic cell lines were compared to those that cause benign chronic infection. Selected rabbit genes including TCR $\gamma$, TCR $\delta$, IL-2R$\alpha$ and CD8$\beta$ were cloned for use as probes for characterization of the lines. Although rabbit CD4+ and CD8+ $\alpha\beta$ T cells can be infected by HTLV-I, CD4-CD8-$\gamma\delta$ T cells predominated in our collection. Even though, the two HTLV-I lines with a leukemogenic effect were $\gamma\delta$ T cells, their lethal nature cannot be attributed solely to their lineage since other $\gamma\delta$ T cells failed to exhibit the same property. The dominance of HTLV-I $\gamma\delta$ T cell lines may be attributable to the high number of $\gamma\delta$ T cells in the rabbit peripheral blood. Since $\gamma\delta$ T cells predominate in rabbit HTLV-I infection, the primary structures of the rabbit TCR $\gamma$ and $\delta$ cDNA clones were determined. Exons 1 and 3 of both TCR $\gamma$ and $\delta$ shared a high degree of identity with their counterparts in other species. By contrast, exon 2 structures of both TCR $\gamma$ and TCR $\delta$ chains were highly divergent among species. Rabbit C$\gamma$ and C$\delta$ exon 2 lack a conserved cysteine residue thought to be responsible for disulfide bond between the TCR $\gamma$ and TCR $\delta$ chain. Two allelic forms of rabbit C$\delta$ were found. One allele has two copies of exon 2 arranged tandemly in the same orientation. Genomic sequence analysis revealed a 464 base pair insertion between C$\delta$ exons 1 and 3. The presence of a duplicate C$\delta$ exon 2 has not been reported for any other species. Availability of these cloned genes provides the groundwork for development of reagents specific for rabbit T cells.
Subject Area
Cellular biology|Microbiology|Veterinary services|Immunology
Recommended Citation
Sawasdikosol, Sansana, "The rabbit model for HTLV-I infection" (1994). Doctoral Dissertations Available from Proquest. AAI9420687.
https://scholarworks.umass.edu/dissertations/AAI9420687