HUMORAL AND CELLULAR IMMUNE-RESPONSES IN RHESUS MACAQUES INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2

Eighteen rhesus macaques were inoculated with either an infectious mol ecularly cloned human immunodeficiency virus type 2 (HIV-2)(SBW/ISY), Or With one of eight mutants defective in one or more accessory genes, The immune responses generated by the macaques were monitored for up to 2 years postinfection, All the macaques except those that received mutants lacking the vpr or vif genes demonstrated low to moderate anti body titers, Macaques inoculated with vpx(-) mutants exhibited a persi stent serological response, suggesting continuous virus expression eve n in the absence of detectable virus in the peripheral blood mononucle ar cells (PBMCs), Neutralizing antibodies developed in only four macaq ues, In general, low-level cytotoxic T lymphocyte (CTL) activity, not clearly HIV-2 specific, was detected in PBMCs, However, one virus-nega tive macaque exhibited significant HIV-2-specific CTL activity in an e nriched CD8(+) cell population from PBMCs, suggesting clearance of the viral infection, In addition, CTL activity against the Env and Gag/Po l epitopes of HIV-2 by CD8(+) lymphocytes from the spleens and lymph n odes of two infected macaques, in one case requiring CD8(+) T cell enr ichment and in the other clearly evident in unfractionated tissue lymp hocytes, was demonstrated for the first time, This sequestration of ti ssue CTLs occurred in the absence of significant levels of circulating CTLs in the blood, Our results suggest that routine monitoring of PBM Cs may sometimes be inadequate for detecting cell-mediated immune resp onses. Elucidation of immune correlates of vaccine protection may ther efore require sampling of lymphoid tissues and assessment of enriched CD8(+) populations.