Studies of cell surface markers for rabbit lymphoid cell populations have continued and progress has been made in several areas of interest. The gene for rabbit CD4 (RbCD4) marker was cloned and was used to verify the specificity of a McAb directed CD4, this has been used to establish normal values for this marker and to monitor rabbits infected with HIV. Significant depletion of CD4 was seen in some infected rabbits. In addition the CD4 gene was used in transfection experiments to determine its efficacy as a receptor for HIV-I. RbCD4 transfectants of the human cell line Raji were compared with this line expressing human CD4. The RbCD4 proved to be poor receptor for HIV-1 and therefore studies of rabbits transgenic with human CD4 have been given priority. Animals have been obtained and shown to express the transgene for HuCD4 on appropriate T cells. Infections of PBMC from the transgenics with various strains of HIV are now underway. Other markers for rabbit lymphoid cell populations were studied and genes encoding them cloned; these include the T cell receptors delta and gamma, CD8beta and IL-2ralpha. It was observed using reagents derived in our studies that all HTLV-I transformed cell lines derived by infection of rabbit PBMC with virus in vitro had a similar phenotype. All were CD4-, CD8-, and TCR gamma. Morphological examination using scanning electron microscopy revealed these to be similar to human gammadelta cells. CD4+ and CD8+ lines were derived from PBMC of HTLV-I infected rabbits and CD4+ TCR alphabeta HTLV-I lines were derived from rabbit thymus eliminating the possibility that the HTLV-I isolates used here transform only CD4-CD8- TCR deltagamma cells. The percentage of deltagamma cells in rabbit PBMC is relatively high (23% in adult rabbits); this with diminution of CD4+ and CD8+ cells in IL-2 supplemented PBMC or thymocyte cultures may account for selection of rabbit HTLV-I infected deltagamma T-cell lines in vitro. The availability of well characterized T cell lines with diverse in vivo effects in the rabbit HTLV-I disease model allows evaluation of roles played by cell type in HTLV-I mediated disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000168-16
Application #
3768739
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code