Open AccessChanges in natural immunity during the course of HIV‐1 infection
Author(s) -
BRENNER B. G.,
GRYLLIS C.,
GORNITSKY M.,
WAINBERG M.A.
Publication year - 1993
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1993.tb07956.x
Subject(s) - lymphokine activated killer cell , immunology , cd8 , cytotoxic t cell , cytolysis , population , cellular immunity , k562 cells , virology , medicine , biology , immune system , interleukin 21 , in vitro , biochemistry , environmental health , leukemia
SUMMARY The role of natural killer (NK) and lymphokine‐activated killer (LAK) cell‐mediated cytotoxiciry in AIDS has yet to be established. The objective of this study was to determine inducible LAK cell responses at different stages of HIV‐1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC‐0) subjects and HIV‐1 individuals who were clinically asymptomatic (Centre for Disease Control group 2, CDC‐2) or symptomatic (CDC‐4) with regard to secondary opportunistic infection (OI). LAK cells were generated upon incubation of PBL with IL‐2 and their cytolysis of K562 and U‐937 targets was determined using chromium release assays. The role of CD8 + lymphocytes as progenitors and effectors of these LAK cell responses was determined by immunomagnetic depletion of CD8 + cells from precursor PBL and LAK cells, respectively. LAK cell‐mediated cytotoxicities in HIV‐1‐infected individuals were reduced compared with scronegativc controls without any corresponding changes in the relative proportions of CD56 + (NK) cells among groups. Depletions of CD8 + subsets from either PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56 + cell in the OI‐CDC‐2 scropositive population. No corresponding changes in LAK activities in seronegative control or HIV + /OI + CDC‐4 groups were observed. Levels of LAK activity against K562 targets in CDC‐0/HIV and CDC‐4/HIV + groups correlated with the percentage of CD56 + LAK cells; corresponding LAK activity in the CDC‐2/HIV + group correlated with the percentage of both CD56 + and CD8 + subsets. These findings suggest that adaptive changes in non‐MHC restricted cytotoxic responses occur in HIV‐1 individuals at early stages post‐HIV infection, before the onset of opportunistic infection.