Potential significance of the cellular immune response against the macaque strain of simian immunodeficiency virus (SIVMAC) in immunized and infected rhesus macaques

Abstract

The cellular immune response of seven rhesus macaques immunized with Tween-ether-treated macaque strain of simian immunodeficiency virus (SIVMAc) and three non-vaccinated control animals was investigated. Immunization elicited antigen-specific proliferating CD4 ÷ cells in five of seven monkeys. Proliferating T cells were found in all animals protected from a first virus challenge. Cytotoxic T lymphocytes (CTLs) were not induced by the immunization. After the second challenge, the four formerly protected animals became infected, despite a strong proliferative CD4 ÷ cell activity in three of them. All animals lost their proliferative activity 2 weeks after infection. After the first challenge four of the six infected animals exhibited a CTL response and after the second challenge, one of four newly infected macaques acquired a CTL response. The five animals with a CTL activity against SIVMAc proteins were protected from severe thrombocytopenia, which appeared in the five CTL-negative animals after infection. Our data show the induction of proliferative T cells by immunization with soluble SIVMAc antigen. This T cell reactivity was found in all animals protected from the first virus challenge, but did not confer protection from the second challenge. Interestingly, the proliferative T cell reactivity disappeared 2 weeks after virus infection. Furthermore a CTL response against viral proteins seems to protect infected animals from severe thrombocytopenia which is an early sign of AIDS in monkeys.

T‐helper reactivity to simian immunodeficiency virus gag synthetic peptides in human immunodeficiency virus type 2 infected individuals

“…In addition, T-cell cross reactivity to HIVB antigens was observed recently in SIV challenged monkeys [Dittmer et al, 19941. On the other hand, it is important to recognize that although protection of SIV vaccinated monkeys was shown to be due in large part to cellular antigens incorporated in the preparations [Stott et al, 1990[Stott et al, , 1991Chan et al, 19921, there is a considerable body of evidence suggesting that virusspecific T-cell immunity plays an important role against infection and disease progression [Voss et al, 1992;Yasutomi et al, 1993;Clerici et al, 1994b;Heeney et al, 1994;Schultz and Stott, 19941. Despite the reduced number of patients investigated here, a statistically significant correlation between the degree of immunodeficiency, as assessed by the levels of CD4+ lymphocytes, and the number of reacting peptides was found.…”

“…Convincing evidence that SIV can infect humans was presented recently in a n SIV laboratory worker who does not show any clinical or laboratory evidence of disease [Khabbaz et al, 19941. In this respect, preinfection of macaques with a non-pathogenic immunodefi-ciency virus (HIVB,,,) could not prevent super infection with SIV,,, but protected against the pathogenic consequences of the latter infection, in which T-helper 1 cells appear to be responsible for protection [Petri et al, 19941. In addition, T-cell cross reactivity to HIVB antigens was observed recently in SIV challenged monkeys [Dittmer et al, 19941. On the other hand, it is important to recognize that although protection of SIV vaccinated monkeys was shown to be due in large part to cellular antigens incorporated in the preparations [Stott et al, 1990[Stott et al, , 1991Chan et al, 19921, there is a considerable body of evidence suggesting that virusspecific T-cell immunity plays an important role against infection and disease progression [Voss et al, 1992;Yasutomi et al, 1993;Clerici et al, 1994b;Heeney et al, 1994;Schultz and Stott, 19941. Despite the reduced number of patients investigated here, a statistically significant correlation between the degree of immunodeficiency, as assessed by the levels of CD4+ lymphocytes, and the number of reacting peptides was found.…”

Construction, replication, and immunogenic properties of a simian immunodeficiency virus expressing interleukin-2

“…b Boldface type indicates lysis which was 10% above the unspecific lysis of wildtype-infected target cells; this degree of lysis was regarded as SIV specific (53).…”

Repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (SIV) did not protect them against the consequences of a high-dose SIV challenge

“…In earlier experiments of our group such proliferating T cells were characterized as CD4 + and depended on MHC class II DR antigen presentation (Voss et al, 1992b(Voss et al, , 1993. In general, the T cell response of the silently infected macaques was weaker than that of macaques immunized with adjuvant-formulated, disrupted SIV (Voss et al, 1992b(Voss et al, , 1993. After a low-dose SIV exposure, specifically proliferating T cells may have been induced by an initial low-level SIV replication or just by an exposure to SIV antigens.…”

“…In our experiment, all silently infected macaques remained clinical healthy and developed an SIV-specific, proliferative T cell response. In earlier experiments of our group such proliferating T cells were characterized as CD4 + and depended on MHC class II DR antigen presentation (Voss et al, 1992b(Voss et al, , 1993. In general, the T cell response of the silently infected macaques was weaker than that of macaques immunized with adjuvant-formulated, disrupted SIV (Voss et al, 1992b(Voss et al, , 1993.…”