Protective cellular retroviral immunity requires both CD4+ and CD8+ immune T cells

Hom, Richard C.; Finberg, Robert W.; Mullaney, Scott; Ruprecht, Ruth M.

doi:10.1128/jvi.65.1.220-224.1991

Cited by 50 publications

(11 citation statements)

References 29 publications

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“…In other experimental situations, sequential actions of CD8 and CD4 subsets may be required for antiviral DTH responses (31), and cooperation of both subsets may be required to protect against infection (32). Different subsets may have different roles at different sites (33,34), and in different genetic strains of animal.…”

Section: Discussionmentioning

confidence: 99%

Distinct types of lung disease caused by functional subsets of antiviral T cells.

Alwan

Kozlowska

Openshaw

1994

The Journal of Experimental Medicine

294

209

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SummaryT cells appear to play a central role in viral bronchiolitis, but the effects of different functional and phenotypic subgroups ofT cells have not been defined. To test the activities ofT cells recognizing individual proteins of respiratory syncytial (RS) virus, virus-specific T cell lines were produced from mice primed by scarification with recombinant vaccinia viruses expressing the major surface glycoprotein (G), fusion protein (F) or second matrix (22K) protein of KS virus. As previously reported, the in vitro characteristics of these cells are predetermined by the choice of KS virus protein: 22K-specific cells are predominantly class I-restricted cytolytic CD8 + cells; F-specific cells, a mixture of cytolytic CD8 + cells and CD4 + cells with a T helper 1 cell (Thl) cytokine secretion profile, whereas those from G-sensitized mice are almost exclusively CD4 + , with Th2 characteristics. Mice infected intranasally with RS virus showed mild illness and recovered fully, but developed respiratory distress after intravenous injections of T cells. Dose-for-dose, infected mice receiving G-specific cells suffered the most severe (sometimes fatal) illness, characterized by lung hemorrhage, pulmonary neutrophil recruitment (shock lung) and intense pulmonary eosinophilia. This disease was further enhanced by coinjection of 22K-specific cells, which alone caused mild shock lung without eosinophilia. F-specific cells caused minimal enhancement of pathology and had little or no effect on the disease caused by G-specific cells. Each cell line reduced lung virus titer and combined injections of G-and 22K-specific cells eliminated infection completely. The in vitro characteristics of these antiviral T cell lines therefore predict the pathological effects in vivo. Moreover, different forms of viral bronchiolitis can be caused by functionally distinct types of activated T cell.

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Section: Discussionmentioning

confidence: 99%

Distinct types of lung disease caused by functional subsets of antiviral T cells.

Alwan

Kozlowska

Openshaw

1994

The Journal of Experimental Medicine

294

209

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“…5). CTL responses have been described during infection with a number of MuLV strains, including Friend (7,9,13,22), Gross (18), and Rauscher (8). However, the role of retrovirus-specific CTL in neurologic disease pathogenesis has been described only for Cas-MuLV (4,21) and ts1 Moloney MuLV (ts1-MuLV) (24) infections.…”

Section: Discussionmentioning

confidence: 99%

Immunogenic determinants of a neuropathogenic murine leukemia virus

Robbins¹,

Remington²,

Sarzotti³

et al. 1995

J Virol

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Previous studies of Cas-Br-M murine leukemia virus (MuLV) (Cas-MuLV) infection demonstrated that cytotoxic T cells (CTL) of the CD8 ؉ phenotype play a role in resistance to the neuropathogenic effects of the virus in NFS/N mice. In the current study, we sought to identify the Cas-MuLV epitopes that are immunogenic for the CTL response. Infection of adult NFS/N mice with a well-characterized neuropathogenic variant of Friend MuLV, PVC-211 MuLV (PVC-MuLV), was not immunogenic for MuLV-specific CTL. Therefore, we constructed chimeric viruses between Cas-MuLV and PVC-MuLV. Infectious chimeras contained the Cas-MuLV env gene on a PVC-MuLV background (PVC-Cas env MuLV) and the PVC-MuLV env gene on a Cas-MuLV background (Cas-PVC env MuLV). Cas-MuLV-specific CTL were found following inoculation of both the chimeric viruses and the parental Cas-MuLV but not the parental PVC-MuLV, despite evidence of antibody responses to both parental and chimeric MuLV. CTL generated in response to infection with PVC-Cas env MuLV and Cas-PVC env MuLV were exclusively of the CD8 ؉ phenotype. These results indicate that both the env and gag-pol regions of Cas-MuLV express epitopes that are immunogenic for CTL. Previous studies of Cas-Br-M murine leukemia virus (MuLV) (Cas-MuLV) infection have demonstrated that immune T cells play a role in resistance to the neuropathogenic effects of the virus (4, 6, 20). CD8 ϩ cytotoxic T cells (CTL) derived from syngeneic mice exposed to Cas-MuLV at 21 days of age conferred resistance to the neuropathogenic effects of Cas-MuLV when transferred into susceptible newborn NFS/N mice (4). However, since protective T-cell immune responses have not been universally demonstrated in mice during the course of other neuropathogenic MuLV infections (5), the Cas-MuLV epitopes immunogenic for CTL induction in adult NFS/N mice may be unique. Since the env sequences have been implicated in the neuropathogenic effects of several MuLV strains (2, 12, 16, 25) and are the least conserved among the MuLV family of retroviruses (17, 20), we focused our attention on the potential immunogenic epitopes within the Cas-MuLV env gene. In this study, chimeric viruses were constructed between Cas-MuLV (10) and PVC 211 MuLV (PVC-MuLV) (12), a neuropathogenic variant of Friend MuLV that did not stimulate the induction of retrovirus-specific CTL. The results of this study demonstrated that Cas-MuLV contains epitopes in the env region and also in the gag-pol region that are immunogenic for CTL in adult NFS/N mice.

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“…T lymphocytes play a vital role in host immunity (4,12,19,20). However, in many viral infections, T cells or their subsets are found to be directly or indirectly responsible for causing the disease rather than preventing it (23,36).…”

Section: Discussionmentioning

confidence: 99%

“…Spleen cells were isolated from tsl-infected mice at 20 days after infection as described above. T-cell subsets were separated as described before (12). Briefly, cells were incubated over a nylon wool column (Cellular Products, Buffalo, N.Y.) at 37°C.…”

Section: Methodsmentioning

confidence: 99%

ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, can infect both CD4+ and CD8+ T cells but requires CD4+ T cells in order to cause paralysis and immunodeficiency

Saha

Wong

1992

J Virol

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When neonatal FVB/N mice were inoculated with tsl, a temperature-sensitive mutant of Moloney murine leukemia virus TB, they developed a progressive bilateral hindlimb paralysis and immunodeficiency leading to death 4 to 6 weeks after inoculation. T lymphocytes have been shown to be primarily responsible for this tsl-induced syndrome. Here we compare the role played by each subset of T lymphocytes, i.e., CD4+ and CD8+ T cells, in disease development. Mice were depleted of a specific subset for the first 10 days of their lives by using either anti-CD4 or anti-CD8 monoclonal antibodies in vivo. Disease development in these mice was then monitored. Depletion of CD4+ T cells significantly attenuated the tsl-induced syndrome: virus replication was decreased, disease latency was extended, and death was prevented in 60% of the mice. Similar treatment with anti-CD8 antibody had almost no effect on disease progression. However, when depletion was begun 2 weeks after neonatal tsl inoculation, CD4+ T cell depletion did not affect disease development. tsl infected CD4+ and CD8+ T lymphocytes equally well in vivo, as shown by flow cytometric analysis, but virus replication was restricted primarily to the CD4+ subset of T cells, as found by in vitro assay. Hence, CD4+ T lymphocytes play an important role in the development of tsl-induced paralysis and immunodeficiency. The mechanism of this CD4+ T-cell-mediated disease production by tsl is not clear; however, increased replication of tsl in the CD4+ T cells, especially in the early stages of the disease, seems to play a crucial role.

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Protective cellular retroviral immunity requires both CD4+ and CD8+ immune T cells

Cited by 50 publications

References 29 publications

Distinct types of lung disease caused by functional subsets of antiviral T cells.

Distinct types of lung disease caused by functional subsets of antiviral T cells.

Immunogenic determinants of a neuropathogenic murine leukemia virus

ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, can infect both CD4+ and CD8+ T cells but requires CD4+ T cells in order to cause paralysis and immunodeficiency

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