HIV DOES NOT REPLICATE IN NAIVE CD4 T-CELLS STIMULATED WITH CD3 CD28/

In this report, we demonstrate that the T cell tropic strain of HIV, L AI, does not replicate in naive CD4 T cells stimulated by cross-linkin g CD3 and CD28. In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way, Unlike this physiologically relevant stim ulation, PHA stimulates productive LAI replication in both naive and m emory T cells, These studies were conducted with highly purified (FACS (R)-isolated) subsets of CD4 T cells identified by expression of both CD45RA and CD62L. Remixing of purified T cells showed that naive T cel ls do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells. The suppression of productive LAI replication in naive T cells is not due to differen tial expression of viral coreceptors, nor is it due to inhibition of a ctivation of the important HIV transcription factors, nuclear factor-k appa B and activator protein-1., The inherent resistance of naive T ce lls to productive HIV infection, coupled with their proliferative adva ntage as demonstrated here, provides a sound basis for proposed clinic al therapies using ex vivo expansion and reinfusion of CD4 T cells fro m HIV-infected adults.