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. 1997 Dec 15;186(12):2063-8.
doi: 10.1084/jem.186.12.2063.

Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice

M B Graham  1 , T J Braciale
Affiliations

Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice

M B Graham et al. J Exp Med. .

"VSports app下载" Abstract

In the adaptive immune response to most viruses, both the cellular and humoral arms of the immune system play complementary roles in eliminating virus and virus-infected cells and in promoting recovery. To evaluate the relative contribution of CD4+ and CD8+ effector T lymphocytes in virus clearance and recovery, we have examined the host response to lethal type A influenza virus infection in B lymphocyte-deficient mice with a targeted disruption in the immunoglobulin mu heavy chain VSports手机版. Our results indicate that naive B cell-deficient mice have a 50- 100-fold greater susceptibility to lethal type A influenza virus infection than do wild type mice. However, after priming with sublethal doses of influenza, immune B cell-deficient animals show an enhanced resistance to lethal virus infection. This finding indicates that an antibody-independent immune-mediated antiviral mechanism accounts for the increased resistance to lethal virus challenge. To assess the contribution of influenza-specific CD4+ and CD8+ effector T cells in this process, defined clonal populations of influenza-specific CD4+ and CD8+ effector T cells were adoptively transferred into lethally infected B cell-deficient mice. Cloned CD8+ effectors efficiently promoted recovery from lethal infection, whereas cloned CD4+ T cells conferred only partial protection. These results suggest that memory T lymphocytes can act independently of a humoral immune response in order to confer resistance to influenza infection in immune individuals. The potential implications of these results for vaccination against human influenza infection are discussed. .

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"V体育平台登录" Figures

Figure 1
Figure 1
B cell–deficient mice are more susceptible to influenza viral challenge. μKO (a) and C57Bl/6 (b) mice were intranasally inoculated with varying doses (♦, 10−3 dilution; ▪, 10−4 dilution; •, 10−5 dilution; ▴, 10−6 dilution; and ✖, 10−7 dilution) of mouse adapted influenza virus and watched for 21 d for morbidity and mortality.
Figure 2
Figure 2
μKO mice can initiate and maintain an influenza-specific CTL response after challenge with influenza virus. (a) Lungs were removed from μKO (shaded bars) and C57BL/6 (open bars) mice on day 12 after intranasal viral challenge with a sublethal dose of A/JAPAN/57 (attenuated strain). Cell suspensions from the lungs were obtained by processing through a sieve, and were Ficoll purified and plated for a final effector/targer (E/T) ratio of 50:1. Assay time was 6 h and spontaneous release for all targets was <20%. Results of two separate experiments with two mice per experimental group are shown. (b) Influenza specific bulks from four individual μKO (shaded bars) and from C57BL/6 (open bars) mice were tested for their ability to lyse uninfected and A/JAPAN/57 infected class II negative (EL4) and class I and II positive (LB15.13) target cells in a standard chromium release assay. Assay time = 6 h; E/T = 10:1. Spontaneous release for all targets was <15%. Experiment is representative of three separate experiments.
Figure 3
Figure 3
B cell–deficient mice are more susceptible to rechallenge with influenza. Groups of 7–12 age-matched μKO (open symbols) and C57Bl/6 (closed symbols) mice were intranasally infected with attenuated A/JAPAN/57. 28 d later the animals were rechallenged intranasally with the dilutions of mouse adapted A/JAPAN/57: ▵, 10−1 dilution; ○, 10−2 dilution; ⋄, 10−3 dilution; □, 10−4 dilution. Animals were followed for 21 d for mortality. Data is representative of two experiments.
Figure 4
Figure 4
CD8+, but not CD4+, T cell clones promote full recovery in B cell–deficient mice. B cell–deficient (μKO) mice were infected intranasally with a 10 LD50 dose of mouse-adapted A/JAPAN/57 virus followed by an intravenous injection of 107 cells. The cells transferred included 4D7 (⋄, a CD4+ clone), 11E4 (▴, a CD8+ clone), and B1.11 (•, a CD8+ clone). Mice receiving intranasal influenza, but no cell transfer, are denoted as □. C57Bl/6 mice receiving intranasal influenza without cell transfer are also shown (✖). Each group represents 5–7 animals. Adoptive transfer of these clones and media control into lethally challenged C57Bl/ 6 mice was done simultaneously as a control.
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References

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