Our studies indicate that the expression obtained appears to be transient 
although in both animals G418-resistant T cells could be obtained as late as 
5-7 months after transplant. The transient expression of vector-derived genes 
in blood cells obtained from the reconstituted animals could be explained by 
any of several possibilities. For exairple, infection might have been 
restricted to the more differentiated bone marrow cells which have a limited 
life span. Alternatively, infection might have been achieved only in a very 
small number of stem cells, with subsequent progressive dilution of these cells 
in the absence of a positive selective growth advantage. It is also possible 
that infected cells undergo cell membrane modification or express extraneous 
neo-antigens that could elicit a response fran activated macrophages, NK cells 
or immune lymphocytes that are regenerating in the irradiated, 
marrow-reconstituted host. Finally, the decline in h-ADA activity could be 
explained by the selective loss of vector sequences due to vector instability, 
by a decrease in the level of expression of the vector genes in individual 
cells over time, or by overproduction of ADA thereby inhibiting or killing 
positive cells. 
Our failure to detect CFCJ-C equally G418-resistant post-transplant as were 
found pre-transplant is also consistent with any of the above hypotheses. The 
detection of G418-resistant clonable T cells in the circulation of animal #56 
at day 181 (Figure 9) and of T cells capable of growth in G418 from animal #57 
at day 230 (Table 3) raises the possibility that long-lived T lymphocytes 
infected with the SAX vector survive for extended periods in these animals. 
Vector gene expression among the animals in our series has not been 
consistent. For example, in monkey #10 h-ADA activity was detected at levels 
20 to 50 fold lower than in monkeys #56 and #57 despite the fact that Southern 
blot analysis of circulating cells detected vector DNA in this animal. Thus, 
[292] Recombinant DNA Research, Volume 12 
