DEVELOPMENT OF AN ANIMAL-MODEL FOR AUTOTRANSFUSION THERAPY - IN-VITROCHARACTERIZATION AND ANALYSIS OF ANTI-CD3 CD28 EXPANDED CELLS/

Previous studies have shown that in vitro culture of human CD4(+) T ce lls with antibodies to CD3 and CD28 immobilized on beads induced an an tiviral effect to HIV-1 infection. Herein, we have used CD4(+) T cells from nonhuman primates to address issues critical for use of such cel ls for therapy and immune reconstitution of humans and nonhuman primat es infected with HIV and simian immunovirus (SIV). These studies inclu de definition of the kinetics of the antiviral effect, the relative st ability of the acquired phenotype, and whether such activated and expa nded CD4+ T cells retain their immune function. Results of our studies show that antiviral effect is induced rapidly following activation wi th anti-CD3/CD28-coated bends. Additionally, the antiviral effect is n ot stable in these cells and requires continuous culture with anti-CD3 /CD28 beads. Removal of CD4(+) T cells from anti-CD3/CD28 stimulation renders these cells susceptible to infection, demonstrating that the r esistant phenotype is not stable in these cultures. However, anti-CD3/ CD28 expanded CD4(+) T cells do retain immune function. Thus, although these findings imply a note of caution for therapeutic strategies aim ed at providing patients with virus-resistant CD4(+) T cells, the pres ent study suggests that transfusion of such cells with retained immune function may have immune restoration capability.