J. Heeney et al., IMMUNE STRATEGIES UTILIZED BY LENTIVIRUS INFECTED CHIMPANZEES TO RESIST PROGRESSION TO AIDS, Immunology letters, 51(1-2), 1996, pp. 45-52
HIV-1 infected chimpanzees are relatively resistant to the development
of AIDS despite their close genetic relatedness to humans and their s
usceptibility to HIV-I infection. We have systematically studied possi
ble reasons for their relative ability to maintain T helper (Th) cell
numbers and immune competence in the presence of chronic HIV-1 infecti
on. Factors which may alone or together cause the loss in T-cell depen
dent immunity include: (i) the loss of Th cell function; (ii) the loss
of Th cells; and (iii) the loss of capacity for Th cell renewal. Diff
erences in the in vivo and in vitro responses of T lymphocytes from ch
impanzees and humans were compared for evidence of HIV-1 related T-cel
l dysfunction. In contrast to HIV infected individuals, HIV-I infected
chimpanzees maintained strong Th cell proliferative and cytokine resp
onses after receiving tetanus toroid boosts. In addition there was no
abnormal Th1 to Th2 shift as is suggested to occur in AIDS patients. T
here was no evidence of Th cell dysfunction such as increased level of
programmed cell death (PCD) or immune activation in HIV-I infected ch
impanzees in contrast to HIV-1 infected asymptomatic humans. Anergy co
uld be induced with HIV-I gp120 in human but not chimpanzee Th lymphoc
ytes. We then asked if there was a direct loss of chimpanzee CD4(+) ce
lls due to HIV-1 infection in vitro. Infection of chimpanzee CD4(+) ly
mphocyte cultures with HIV-1 in the absence of CD8(+) cells resulted i
n marked cytopathic effect with complete lysis and loss of cells withi
n 3 weeks. We concluded that most chronic HIV-I infected chimpanzees w
ere able to maintain relatively stable CD4(+) lymphocyte numbers despi
te CD4(+) lymphocyte destruction due to direct effects of the virus. F
urthermore, there was no evidence of indirect Th cell loss, since neit
her increased levels of anergy nor apoptosis were observed. Lymph node
biopsies from HIV-1 infected chimpanzees revealed that MHC class II r
ich regions of lymph nodes remained intact, in contrast to the involut
ion of these regions in infected humans. This suggested that chimpanze
es may maintain the capacity for Th cell renewal by preserving this MH
C class II lymphoid environment. The data presented in this paper sugg
ests that chimpanzees may preserve this critical MHC class II-Th cell
environment by dramatically suppressing extra-cellular virus load and
that this may be in part mediated by soluble lentivirus suppressing fa
ctors.