Abstract
To determine the role of respiratory syncytial virus (RSV)-specific cell-mediated immunity during natural reinfection, we investigated whether RSV-specific T-cell responses protect against reinfection and, subsequently, whether reinfection boosts virus-specific memory. In a cohort of 55 infants who were hospitalized for RSV bronchiolitis, RSV-specific lymphoproliferative responses in the peripheral blood were measured at three time-points: on admission, 4 wk after admission, and 1 y later, after the second winter season. Memory was defined as a stimulation index (SI) >2. During the second winter season, nasal secretions were collected in every case of a runny nose. Reinfection was diagnosed if immunofluorescence or PCR was positive for RSV. Virus-specific memory was found in one child on admission for primary RSV infection, whereas 4 wk later 44 infants (80%) had memory. Reinfection with RSV was found in 23 infants (43%) during the second winter season. After the second season, memory was found in 20 infants (38%). No differences in SI after the second winter season were found between infants with and without reinfection (2.3 versus 2.1). However, a highly significant correlation was found between SI measured 4 wk after primary RSV infection and SI after the second winter season (r = 0.40, p = 0.001). In conclusion, RSV-specific T-cell responses did not provide protection against reinfection. Moreover, reinfection did not boost RSV-specific T-cell proliferation. To explain both findings, it is hypothesized that RSV-specific T cells fail to expand in vivo upon reinfection.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- RSV:
-
respiratory syncytial virus
- CMI:
-
cell-mediated immunity
- RT-PCR:
-
reverse transcriptase PCR
- TCID:
-
tissue culture infection dose
- LPR:
-
lymphoproliferative response
- IFN:
-
interferon
References
Karron RA, Singleton RJ, Bulkow L, Parkinson A, Kruse D, DeSmet I, Indorf C, Petersen KM, Leombruno D, Hurlburt D, Santosham M, Harrison LH 1999 Severe respiratory syncytial virus disease in Alaska native children. RSV Alaska Study Group. J Infect Dis 180: 41–49
Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ 1999 Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA 282: 1440–1446
Wang EEL, Law BJ 1998 Respiratory syncytial virus infection in pediatric patients. Semin Pediatr Infect Dis 9: 146–153
Outwater KM, Crone RK 1984 Management of respiratory failure in infants with acute viral bronchiolitis. Am J Dis Child 138: 1071–1075
Frankel LR, Lewiston NJ, Smith DW, Stevenson DK 1986 Clinical observations on mechanical ventilation for respiratory failure in bronchiolitis. Pediatr Pulmonol 2: 307–311
Tissing WJE, Van Steensel-Moll HA, Offringa M 1993 Risk factors for mechanical ventilation in respiratory syncytial virus infection. Eur J Pediatr 152: 125–127
Shay DK, Holman RC, Roosevelt GE, Clarke MJ, Anderson LJ 2000 Bronchiolitis-associated mortality estimates of respiratory syncytial virus-associated deaths among US children, 1979–1997. J Infect Dis 183: 16–22
Henderson FW, Collier AM, Clyde WA Jr, Denny FW 1979 Respiratory-syncytial-virus infections, reinfections immunity. A prospective, longitudinal study in young children. N Engl J Med 300: 530–534
Hall CB, Walsh EE, Long CE, Schnabel KC 1991 Immunity to frequency of reinfection with respiratory syncytial virus. J Infect Dis 163: 693–698
Graham BS, Bunton LA, Wright PF, Karzon DT 1991 Role of T lymphocyte subsets in the pathogenesis of primary infection rechallenge with respiratory syncytial virus in mice. J Clin Invest 88: 1026–1033
Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE 1969 An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 89: 405–421
Graham BS 1995 Pathogenesis of respiratory syncytial virus vaccine-augmented pathology. Am J Respir Crit Care Med 152: S63–S66
Plotnicky-Gilquin H, Huss T, Aubry JP, Haeuw JF, Beck A, Bonnefoy JY, Nguyen TN, Power UF 1999 Absence of lung immunopathology following respiratory syncytial virus (RSV) challenge in mice immunized with a recombinant RSV G protein fragment. Virology 258: 128–140
Groothuis JR, King SJ, Hogerman DA, Paradiso PR, Simoes EAF 1998 Safety immunogenicity of a purified F protein respiratory syncytial virus (PFP-2) vaccine in seropositive children with bronchopulmonary dysplasia. J Infect Dis 177: 467–469
Piedra PA, Grace S, Jewell A, Spinelli S, Hogerman DA, Malinoski F, Hiatt PW 1998 Sequential annual administration of purified protein vaccine against respiratory syncytial virus in children with cystic fibrosis. Pediatr Infect Dis J 17: 217–224
Waris ME, Tsou C, Erdman DD, Day DB, Anderson LJ 1997 Priming with live respiratory syncytial virus (RSV) prevents the enhanced pulmonary inflammatory response seen after RSV challenge in BALB/c mice immunized with formalin-inactivated RSV. J Virol 71: 6935–6939
Stein RT, Sherill D, Morgan WJ, Holberg CJ, Halonen M, Taussig LM, Wright AL, Martinez FD 1999 Respiratory syncytial virus in early life risk of wheeze allergy by age 13. Lancet 354: 541–545
Boom R, Sol CJ, Salimans MM, Jansen CL, Wertheim-van Dillen PM, van der Noordaa J 1990 Rapid simple method for purification of nucleic acids. J Clin Microbiol 28: 495–503
Nijhuis M, Boucher CA, Schuurman R 1995 Sensitive procedure for the amplification of HIV-1 RNA using a combined reverse-transcription amplification reaction. Biotechniques 19: 178–180, 182
Lennette EH, Schmidt NJ 1979 Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections, 5th Ed. American Public Health Association, Washington, DC, 19–21
Scott R, Kaul A, Scott M, Chiba Y, Ogra PL 1978 Development of in vitro correlates of cell-mediated immunity to respiratory syncytial virus infection in humans. J Infect Dis 137: 810–817
Welliver RC, Kaul A, Ogra PL 1979 Cell-mediated immune response to respiratory syncytial virus infection: relationship to the development of reactive airway disease. J Pediatr 94: 370–375
Hall CB, Geiman JM, Biggar R, Kotok DI, Hogan PM, Douglas GR 1976 Respiratory syncytial virus infections within families. N Engl J Med 294: 414–419
Fernald GW, Almond JR, Henderson FW 1983 Cellular humoral immunity in recurrent respiratory syncytial virus infection. Pediatr Res 17: 753–758
The IMpact-RSV study group 1998 Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102: 531–537
The PREVENT Study Group 1997 Reduction of respiratory syncytial virus hospitalization among premature infants infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics 99: 93–99
Welliver RC, Tristram DA, Batt K, Sun M, Hogerman DA, Hildreth S 1994 Respiratory syncytial virus-specific cell-mediated immune responses after vaccination with a purified fusion protein subunit vaccine. J Infect Dis 170: 425–428
Michaels MG, Serdy C, Barbadora K, Green M, Apalsch A, Wald ER 1992 Respiratory syncytial virus: a comparison of diagnostic modalities. Pediatr Infect Dis J 11: 613–616
Bangham CR, McMichael AJ 1986 Specific human cytotoxic T cells recognize B-cell lines persistently infected with respiratory syncytial virus. Proc Natl Acad Sci U S A 83: 9183–9187
Isaacs D, Bangham CRM, McMichael AJ 1987 Cell-mediated cytotoxic response to respiratory syncytial virus in infants with bronchiolitis. Lancet 2: 769–771
Kulkarni AB, Connors M, Firestone CY, Morse HC III, Murphy BR 1993 The cytolytic activity of pulmonary CD8+ lymphocytes induced by infection with a vaccinia virus recombinant expressing the M2 protein of respiratory syncytial virus (RSV), correlates with resistance to RSV infection in mice. J Virol 67: 1044–1049
Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP 1999 Natural killer cells in antiviral defense: function regulation by innate cytokines. Annu Rev Immunol 17: 189–220
Anderson JJ, Serin M, Harrop J, Amin S, Toms GL, Scott R 1989 Natural killer cell response to respiratory syncytial virus in the Balb/c mouse model. Adv Exp Med Biol 257: 211–220
Hussell T, Openshaw PJ 1998 Intracellular IFN-gamma expression in natural killer cells precedes lung CD8+ T cell recruitment during respiratory syncytial virus infection. J Gen Virol 79 ( Pt 11): 2593–2601
Garofalo RP, Mei F, Espejeo R, Ye G, Haeberle H, Baron S, Ogra PL, Reyes VE 1996 Respiratory syncytial virus infection of human respiratory epithelial cells up-regulates class 1 MHC expression through the induction of IFN-beta IL-1-alpha. J Immunol 157: 2506–2513
Nakayama T, Sonoda S, Urano T, Sasaki K, Maehara N, Makino S 1993 Detection of alpha-interferon in nasopharyngeal secretions sera in children infected with respiratory syncytial virus. Pediatr Infect Dis J 12: 925–929
Acknowledgements
The authors thank Dr. A.M. van Loon (University Medical Center, Utrecht, The Netherlands) for providing facilities to prepare RSV. We also thank Mrs. J. Zijlstra and Mrs. M. Ringeling-Van der Pol (University Medical Center, Utrecht, The Netherlands) for excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the Dutch Asthma Foundation (grant number 32.96.08).
Rights and permissions
About this article
Cite this article
Bont, L., Versteegh, J., Swelsen, W. et al. Natural Reinfection with Respiratory Syncytial Virus Does Not Boost Virus-Specific T-Cell Immunity. Pediatr Res 52, 363–367 (2002). https://doi.org/10.1203/00006450-200209000-00009
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-200209000-00009
This article is cited by
-
Current State of Respiratory Syncytial Virus Disease and Management
Infectious Diseases and Therapy (2021)
-
Healthcare resource use and economic burden attributable to respiratory syncytial virus in the United States: a claims database analysis
BMC Health Services Research (2018)
-
Systems biology from virus to humans
Journal of Analytical Science and Technology (2015)
-
Human memory T cells: generation, compartmentalization and homeostasis
Nature Reviews Immunology (2014)
