IMMUNE STRATEGIES UTILIZED BY LENTIVIRUS INFECTED CHIMPANZEES TO RESIST PROGRESSION TO AIDS

Citation
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
Citations number
30
Categorie Soggetti
Immunology
Journal title
ISSN journal
01652478
Volume
51
Issue
1-2
Year of publication
1996
Pages
45 - 52
Database
ISI
SICI code
0165-2478(1996)51:1-2<45:ISUBLI>2.0.ZU;2-9
Abstract
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.