MECHANISMS OF PROTECTION INDUCED BY ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS II - LYMPHOCYTE DEPLETION DOES NOT ABROGATE PROTECTION

To determine the role that cellular immune responses play in the prote ction conferred by vaccination with attenuated SIVmac32H (pC8), we hav e attempted to deplete macaques of their CD8(+) cells prior to challen ge with wild-type SIVmac32H (pJ5), In two of four pC8-infected macaque s, N109 and N112, a transient partial depletion of CD8(+) cells by ant ibody treatment was achieved. On the day of challenge peripheral CD2()CD4(-)CD8(+) cell counts were reduced by 92 and 95%, respectively, in animals N109 and N112 and their lymph nodes revealed a 46 and 58% red uction, respectively, in CD2(+)CD4(-)CD8(+) cells. Two other pC8-immun ized macaques, N110 and N111, treated in the same way, did not show si gnificant depletion of CD8(+) cells. None of these four pC8-immunized animals became infected when challenged with 50 MID50 Of pJ5, Treatmen t of a further four pC8-infected and protected macaques and two naive control animals with Campath-1H antibody successfully depleted periphe ral CD3(+) cell counts by >99% in all treated animals. Campath-1H depl etion resulted in enhanced, longer lasting lymphoid depletion. Yet sub sequent challenge with 20 MID50 of pJ5 still failed to infect the pC8- immunized animals. All eight of the naive controls, including two Camp ath-1H-treated animals, became infected following challenge. In summar y, partial depletion of circulating CD8(+) cells or total lymphocytes prior to challenge failed to abrogate the protection conferred by vacc ination with pC8.