Studies of cell surface markers for rabbit lymphoid cell populations have emphasized rabbit T cells with special reference to those involved in retrovirus infection. We have previously derived HTLV-1 transformed cell lines that differ in their pathogenic potential:one cell line (RH/K34) causes an ATLL like disease and death in rabbits, whereas the other (RH/K30) induces a latent infection. The lethal cell line (RH/K34) induces thymocyte depletion and virus produced by this cell line causes apoptosis of human and rabbit lymphocytes. In contrast, the virus purified from the RH/K30 cell line induces proliferation. Rabbit CD4 (RbCD4) transfectants of human and mouse cell lines were compared with these lines expressing human CD4 (HuCD4). RbCD4 proved to be a poor receptor for HIV-1 and therefore rabbits transgenic for human CD4 were developed. Transgenic animals have been obtained and shown to express HuCD4 on appropriate T lymphocyte populations and in a developmentally specific fashion. Infections of PBMC from the transgenics with HIV-1 are more productive than normal rabbit infection. Experiments using human, rabbit or mouse cell lines transfected with HUCD4 or RbCD4, and infected with inactivated or non-inactivated HIV-1 indicate that productive HIV-1 infection is necessary to trigger the apoptotic mechanism. The expression of FAS antigen was significantly increased in HIV-1 infected PBMC from HuCD4 transgenic, but not normal rabbits. Other rabbit lymphoid cell markers investigated include the gd T cell receptors, CD8beta and IL-2Ralpha. Transcripts of the delta TCR gene occurred in two distinct forms, a duplication of exon 2 of the constant region was found in the larger message. This was shown to result from a genetic polymorphism in which the gene encoding TCR Cdelta was duplicated along with some flanking intron sequences. This insertion deletion polymorphism (IDRP) was shown to be inherited as an autosomal codominant trait and animals homozygous for the inserted form had levels of gd T cells in their peripheral blood that were equal to rabbits homozygous for the shorter form. Present studies continue to characterize T cell surface markers that may play a role in pathogenic effects of HTLV-I and HIV-1 infected cells.
