F. Diazmitoma et al., EXPRESSION OF IL-10, IL-4 AND INTERFERON-GAMMA IN UNSTIMULATED AND MITOGEN-STIMULATED PERIPHERAL-BLOOD LYMPHOCYTES FROM HIV-SEROPOSITIVE PATIENTS, Clinical and experimental immunology, 102(1), 1995, pp. 31-39
Infection of immune cells with HIV induces dysregulation of cytokines
which may play a vital role in HIV pathogenesis. We analysed the expre
ssion of T helper type 1 (Thl) (interferon-gamma (IFN-gamma)) and Th2
(IL-4, IL-10) type cytokines in peripheral blood lymphocytes (PBL) fro
m HIV+ patients. The semiquantitative reverse transcriptase polymerase
chain reaction (RT-PCR) analysis revealed that IFN-gamma mRNA in unst
imulated PBL was significantly decreased and IL-IO mRNA was significan
tly upregulated in patients with < 400 CD4(+) T cells/mm(3) (n = 30) a
s compared to patients with > 400 CD4(+) T cells/mm(3) (n = 6) and nor
mal controls (n = 16). In addition, IL-10 mRNA levels were inversely a
ssociated with IFN-gamma expression. Similar results were obtained by
measuring IL-IO production in the supernatants of PBL cultured in vitr
o without stimulation by employing an enzyme immunosorbent assay (ELIS
A). However, the levels of IL-4 and IFN-gamma produced by unstimulated
PBL were undetectable by ELISA. Mitogen stimulation of PBL revealed t
wo groups of HIV+ individuals based on IL-10 production. PBL from one
set of individuals produced low levels of IL-10 (low IL-IO producers)
whereas the other group produced IL-IO comparable to that of normal co
ntrols (IL-10 producers). Production of IL-4 was significantly reduced
in HIV+ individuals with < 400 CD4(+) T cells/mm(3) as compared to th
e normal controls. However, ability to produce IFN-gamma by mitogen-st
imulated total PBL and CD4(+) purified cells was not impaired in HIVindividuals. These results suggest that unstimulated and mitogen-stimu
lated PBL of HIV+ individuals exhibit dysregulation of Th2 type cytoki
nes which may play a role in HIV immunopathogenesis.