Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1997 Jun 24;94(13):6874-9.
doi: 10.1073/pnas.94.13.6874.

A critical role for neutralizing-antibody-producing B cells, CD4(+) T cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: implications for adoptive immunotherapy of virus carriers

O Planz  1 , S Ehl, E Furrer, E Horvath, M A Bründler, H Hengartner, R M Zinkernagel
Affiliations

A critical role for neutralizing-antibody-producing B cells, CD4(+) T cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: implications for adoptive immunotherapy of virus carriers

O Planz et al. Proc Natl Acad Sci U S A. .

Abstract

This study demonstrates that neutralizing-antibody-producing B cells, CD4(+) T cells, and interferons (IFNs) are of key importance in virus control both in adoptive immunotherapy of persistent infection and in the late phase of acute infection with the WE strain of lymphocytic choriomeningitis virus (LCMV). We report the following results. (i) Clearance of LCMV-WE from C57BL/6 carrier mice by adoptive transfer of memory spleen cells requires B cells and CD4(+) T cells but not necessarily CD8(+) T cells. (ii) At the doses examined, CD8(+) T cells contribute to the initial reduction of viral titers but are alone not sufficient to clear the virus because they are exhausted. (iii) In the presence of functional IFN-gamma, virus clearance correlates well with the generation of neutralizing antibodies in the treated carrier mice. (iv) In the absence of receptors for IFN-gamma, virus clearance is not achieved. (v) Adoptive immunotherapy of mice persistently infected with a distinct virus isolate, LCMV-Armstrong, revealed only low levels of neutralizing antibodies; in this case, CD8(+) T cells were needed for virus clearance in addition to B and CD4(+) T cells. (vi) After low dose infection of C57BL/6 mice with LCMV-WE, virus is eliminated below detectable levels by CD8(+) T cells, but long-term (>2 months) virus control is usually not achieved in the absence of B cells or CD4(+) T cells; reappearance of the virus is paralleled either by exhaustion of virus-specific cytotoxic T lymphocytes or lethal immunopathology. These findings are of importance for adoptive immunotherapy strategies against persistent virus infections in humans.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Delayed virus clearance after adoptive transfer of d60 immune spleen cells depleted of CD8+ T cells. LCMV-WE-immune (200 pfu i.v. >60 days previously) spleen cells were depleted of CD4+ (✚) or CD8+ T cells (▪); 108 cells were adoptively transferred into LCMV-WE-carrier mice. Virus clearance in the blood was compared with LCMV-WE-carrier mice receiving 108 untreated d60 immune spleen cells (▴). Titers are expressed as the mean of 7–9 mice; SEM was <0,4 log10.
Figure 2
Figure 2
Neutralizing antibodies are more efficiently induced in LCMV-carrier mice by adoptive transfer of LCMV-WE-primed than LCMV-ARM-primed memory spleen cells. LCMV-WE-immune (▪) or LCMV-ARM-immune (✚) spleen cells (108) were adoptively transferred into the corresponding C57BL/6 LCMV-carrier mice. Sera were analyzed for neutralizing antibody activity (data are the mean of 3–5 mice; SEM < 1). The experiment was repeated four times with similar results.
Figure 3
Figure 3
Long-term virus control after LCMV infection depends on the presence of B cells and CD4+ T cells. IgM −/− and CD4- and MHC class II-deficient mice were infected with low (102 pfu) or intermediate (104 pfu) doses of LCMV-WE, and virus titers were measured in the blood (mean of three to six mice; SEM < 0,5 log10). The experiment was repeated twice with similar results. Within the indicated time intervals, two to three mice per group were killed and spleen cells were tested for LCMV-specific cytotoxicity after 5 days of restimulation with LCMV-infected peritoneal macrophages. Spontaneous 51Cr release was <25% in all assays. Open symbols represent CTL activity from mice in which LCMV reappeared, and solid symbols represent CTL activity from mice in which no virus could be detected.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cole G A, Nathanson N, Prendergast R A. Nature (London) 1972;238:335–337. - PubMed
    1. Doherty P C, Zinkernagel R M. Transplant Rev. 1974;19:89–120. - PubMed
    1. Zinkernagel R M, Welsh R M. J Immunol. 1976;117:1495–1502. - PubMed
    1. Hotchin J. Cold Spring Harbor Symp Quant Biol. 1962;27:479–501. - PubMed
    1. Buchmeier M J, Welsh R M, Dutko F J, Oldstone M B A. Adv Immunol. 1980;30:275–331. - PubMed

Publication types

MeSH terms