INTERLEUKIN-2-INDUCIBLE NATURAL IMMUNE (LYMPHOKINE-ACTIVATED KILLER-CELL) RESPONSES AS A FUNCTIONAL CORRELATE OF PROGRESSION TO AIDS

The functions of natural killer (NK) cells and their interleukin-2-ind ucible counterparts, lymphokine-activated killer (LAK) cells, are ofte n impaired in human immunodeficiency virus (HIV)-infected individuals. A statistical approach was used to establish if changes in WC activit y were associated with antiviral drug therapy, HIV-1 burden, or lympho cyte subset alterations. Our study group included 61 HIV-positive subj ects without any opportunistic infections (OI-), 16 of whom received z idovudine (AZT), and 97 HIV-positive individuals with AIDS-related inf ection (OI+), 50 of whom received AZT. As expected, there was a stepwi se decrease in total lymphocyte numbers in OI+ groups as a result of t he selective loss of CD4(+) cells. The groups receiving AZT therapy ha d fewer CD4(+) cells but lower circulating p24 antigen levels than cor responding untreated groups did. No significant changes in the relativ e proportions or absolute numbers of CD56(+) subsets in HIV-positive g roups could be ascribed to OI status or AZT intervention. LAT cell cyt otoxic responses, measured as LU(20) values (which give a measure of 2 0% cytolysis of target cells), lysis per unit CD56(+) NK cell, or lysi s per unit blood volume, declined in OI+ groups. No main or interactiv e effects of AZT therapy on LAK activities were observed. Multivariate general linear models were used to determine the interactive effects of NK- and T-cell subsets on measured LAX cell responses against K-562 and U-937 targets. CD56(+) and CD4(+) cell numbers were the principal variables that predicted U-937 or K-562 target cell lysis (r = 0.8). p24 antigenemia and CD57(+) LAIC cell numbers were added negative and positive predictors of Wt activity, respectively. These findings indic ate that declines in NK-mediated LAK cell responses serve as functiona l correlates of progression in HIV-infected individuals.