Limits...
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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199163&req=5

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.

Mentions: Fig. 3 shows the results of this priming/challenge study. As expected, conventional mice, which have neutralizing antiviral antibody both in the circulation and locally in the respiratory tract, were uniformly resistant to lethal infection with mouse-adapted virus at virus doses up to 106 EID50 units (i.e., the equivalent of an innoculum of 103 LD50 doses for a naive conventional mouse). By contrast, challenge infection of B lymphocyte–deficient μKO mice resulted in death (Fig. 3). However, the immune μKO mice demonstrated a 100-fold greater resistance to challenge infection with mouse-adapted virus than did naive μKO mice (LD50 values of 101.7 EID50 units and 104 EID50 units for mouse-adapted virus in naive and vaccinated μKO mice, respectively). These results suggest that the enhanced resistance to lethal virus challenge observed in the primed B cell–deficient mice was due to the activation of virus-specific memory T lymphocytes in response to challenge infection.


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 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.
© Copyright Policy
Related In: Results  -  Collection

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

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.
Mentions: Fig. 3 shows the results of this priming/challenge study. As expected, conventional mice, which have neutralizing antiviral antibody both in the circulation and locally in the respiratory tract, were uniformly resistant to lethal infection with mouse-adapted virus at virus doses up to 106 EID50 units (i.e., the equivalent of an innoculum of 103 LD50 doses for a naive conventional mouse). By contrast, challenge infection of B lymphocyte–deficient μKO mice resulted in death (Fig. 3). However, the immune μKO mice demonstrated a 100-fold greater resistance to challenge infection with mouse-adapted virus than did naive μKO mice (LD50 values of 101.7 EID50 units and 104 EID50 units for mouse-adapted virus in naive and vaccinated μKO mice, respectively). These results suggest that the enhanced resistance to lethal virus challenge observed in the primed B cell–deficient mice was due to the activation of virus-specific memory T lymphocytes in response to challenge infection.

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