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

Graham MB, Braciale TJ - J. Exp. Med. (1997)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. mbgraham@uic.edu

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. 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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Related in: MedlinePlus

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.
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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.

Mentions: To assess the impact of the presence or absence of B cells on susceptibility to infection with influenza virus, cohorts of age-matched C57Bl/6 and μKO mice were inoculated intranasally with varying doses of infectious mouse-adapted A/JAPAN/57 influenza virus (10−3–10−7 dilutions of a stock preparation with an infectious titer of 107 EID50/ml in embryonated eggs). As shown in Fig. 1, μKO mice were ∼100-fold more susceptible to lethal virus infection than were wild-type C57Bl/6 mice. The LD50 of this mouse-adapted A/JAPAN/57 influenza virus was 103.8 EID50 units in wild-type C57Bl/6 mice and 101.7 EID50 units in μKO mice, respectively. The titer of mouse-adapted virus used for these studies was ∼107 EID50 units, which corresponds to an LD50 of 103 EID50 units in C57Bl/6 mice and an LD50 of 101–102 EID50 units in μKO mice.


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

Graham MB, Braciale TJ - J. Exp. Med. (1997)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199163&req=5

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.
Mentions: To assess the impact of the presence or absence of B cells on susceptibility to infection with influenza virus, cohorts of age-matched C57Bl/6 and μKO mice were inoculated intranasally with varying doses of infectious mouse-adapted A/JAPAN/57 influenza virus (10−3–10−7 dilutions of a stock preparation with an infectious titer of 107 EID50/ml in embryonated eggs). As shown in Fig. 1, μKO mice were ∼100-fold more susceptible to lethal virus infection than were wild-type C57Bl/6 mice. The LD50 of this mouse-adapted A/JAPAN/57 influenza virus was 103.8 EID50 units in wild-type C57Bl/6 mice and 101.7 EID50 units in μKO mice, respectively. The titer of mouse-adapted virus used for these studies was ∼107 EID50 units, which corresponds to an LD50 of 103 EID50 units in C57Bl/6 mice and an LD50 of 101–102 EID50 units in μKO mice.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. mbgraham@uic.edu

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. 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.

Show MeSH
Related in: MedlinePlus