Virus-specific memory and effector T lymphocytes exhibit different cytokine responses to antigens during experimental murine respiratory syncytial virus infection.
Mice sensitized to the G (attachment) or F (fusion) glycoproteins of respiratory syncytial virus (RSV) expressed different patterns of cytokine production and lung pathology when challenged by intranasal infection with RSV. Five days after challenge, mice sensitized to G glycoprotein produced high levels of interleukin-4 (IL-4) and IL-5 in the lungs and spleens and developed extensive pulmonary eosinophilia, while mice sensitized to F glycoprotein produced IL-2 and developed a mononuclear cell infiltration. Memory lymphocytes isolated 2 weeks after intranasal challenge of mice primed to the G or F glycoprotein secreted only IL-2 and gamma interferon (IFN-gamma) when stimulated with RSV. IL-4 and IL-5 production characteristic of Th2-type effectors in the lung was observed only after multiple rounds of in vitro stimulation of RSV G-specific memory T lymphocytes with antigen. Also IFN-gamma production appeared to play only a minor role in the expression of pulmonary pathology characteristic of Th1 or Th2 T-lymphocyte responses, because mice genetically deficient in IFN-gamma production by gene disruption displayed the same pattern of pulmonary inflammation to RSV infection after priming to RSV F or G as conventional mice. These results suggest that effector T lymphocytes exhibit a different pattern of cytokine production than memory T-lymphocyte precursors precommitted to a Th1 or Th2 pattern of differentiation. Furthermore, these observations raise the possibility that the cytokine response of human memory T lymphocytes after a single exposure to antigen in vitro may not accurately reflect the cytokine response of differentiated effector T lymphocytes at the site of infection in vivo.
Srikiatkhachorn
A
A
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908, USA. as7a@virginia.edu
Braciale
T J
TJ
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D016207:Cytokines / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D015707:HN Protein; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D016207:Cytokines; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D007371:Interferon-gamma