• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. Oct 1, 1994; 180(4): 1273–1282.
PMCID: PMC2191682

Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection

Abstract

T lymphocytes play a primary role in recovery from viral infections and in antiviral immunity. Although viral-specific CD8+ and CD4+ T cells have been shown to be able to lyse virally infected targets in vitro and promote recovery from lethal infection in vivo, the role of CD4+ T lymphocytes and their mechanism(s) of action in viral immunity are not well understood. The ability to further dissect the role that CD4+ T cells play in the immune response to a number of pathogens has been greatly enhanced by evidence for more extensive heterogeneity among the CD4+ T lymphocytes. To further examine the role of CD4+ T cells in the immune response to influenza infection, we have generated influenza virus-specific CD4+ T cell clones from influenza-primed BALB/c mice with differential cytokine secretion profiles that are defined as T helper type 1 (Th1) clones by the production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), or as Th2 clones by the production of IL-4, IL-5, and IL-10. Our studies have revealed that Th1 clones are cytolytic in vitro and protective against lethal challenge with virus in vivo, whereas Th2 clones are noncytolytic and not protective. Upon further evaluation of these clonal populations we have shown that not only are the Th2 clones nonprotective, but that pulmonary pathology is exacerbated as compared with control mice as evidenced by delayed viral clearance and massive pulmonary eosinophilia. These data suggest that virus-specific CD4+ T cells of the Th2 subset may not play a primary role in virus clearance and recovery and may lead to immune mediated potentiation of injury.

Full Text

The Full Text of this article is available as a PDF (4.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bukowski JF, Welsh RM. Inability of interferon to protect virus-infected cells against lysis by natural killer (NK) cells correlates with NK cell-mediated antiviral effects in vivo. J Immunol. 1985 Nov;135(5):3537–3541. [PubMed]
  • Doherty PC, Allan W, Eichelberger M, Carding SR. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Annu Rev Immunol. 1992;10:123–151. [PubMed]
  • Yap KL, Ada GL. The recovery of mice from influenza virus infection: adoptive transfer of immunity with immune T lymphocytes. Scand J Immunol. 1978;7(5):389–397. [PubMed]
  • Yap KL, Braciale TJ, Ada GL. Role of T-cell function in recovery from murine influenza infection. Cell Immunol. 1979 Mar 15;43(2):341–351. [PubMed]
  • Lin YL, Askonas BA. Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions. J Exp Med. 1981 Aug 1;154(2):225–234. [PMC free article] [PubMed]
  • Taylor PM, Askonas BA. Diversity in the biological properties of anti-influenza cytotoxic T cell clones. Eur J Immunol. 1983 Sep;13(9):707–711. [PubMed]
  • Lukacher AE, Braciale VL, Braciale TJ. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med. 1984 Sep 1;160(3):814–826. [PMC free article] [PubMed]
  • Wong GH, Goeddel DV. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. Nature. 323(6091):819–822. [PubMed]
  • Taylor PM, Esquivel F, Askonas BA. Murine CD4+ T cell clones vary in function in vitro and in influenza infection in vivo. Int Immunol. 1990;2(4):323–328. [PubMed]
  • Eichelberger M, Allan W, Zijlstra M, Jaenisch R, Doherty PC. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med. 1991 Oct 1;174(4):875–880. [PMC free article] [PubMed]
  • Palladino G, Scherle PA, Gerhard W. Activity of CD4+ T-cell clones of type 1 and type 2 in generation of influenza virus-specific cytotoxic responses in vitro. J Virol. 1991 Nov;65(11):6071–6076. [PMC free article] [PubMed]
  • Scherle PA, Palladino G, Gerhard W. Mice can recover from pulmonary influenza virus infection in the absence of class I-restricted cytotoxic T cells. J Immunol. 1992 Jan 1;148(1):212–217. [PubMed]
  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed]
  • Boom WH, Liano D, Abbas AK. Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes. J Exp Med. 1988 Apr 1;167(4):1350–1363. [PMC free article] [PubMed]
  • Cher DJ, Mosmann TR. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987 Jun 1;138(11):3688–3694. [PubMed]
  • Scott P, Natovitz P, Coffman RL, Pearce E, Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. [PMC free article] [PubMed]
  • Scott P, Pearce E, Cheever AW, Coffman RL, Sher A. Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. Immunol Rev. 1989 Dec;112:161–182. [PubMed]
  • Reiner SL, Zheng S, Wang ZE, Stowring L, Locksley RM. Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection. J Exp Med. 1994 Feb 1;179(2):447–456. [PMC free article] [PubMed]
  • Kanagawa O, Vaupel BA, Gayama S, Koehler G, Kopf M. Resistance of mice deficient in IL-4 to retrovirus-induced immunodeficiency syndrome (MAIDS) Science. 1993 Oct 8;262(5131):240–242. [PubMed]
  • Clerici M, Hakim FT, Venzon DJ, Blatt S, Hendrix CW, Wynn TA, Shearer GM. Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals. J Clin Invest. 1993 Mar;91(3):759–765. [PMC free article] [PubMed]
  • Alwan WH, Kozlowska WJ, Openshaw PJ. Distinct types of lung disease caused by functional subsets of antiviral T cells. J Exp Med. 1994 Jan 1;179(1):81–89. [PMC free article] [PubMed]
  • Braciale TJ. Immunologic recognition of influenza virus-infected cells. I. Generation of a virus-strain specific and a cross-reactive subpopulation of cytotoxic T cells in the response to type A influenza viruses of different subtypes. Cell Immunol. 1977 Oct;33(2):423–436. [PubMed]
  • Kim KJ, Kanellopoulos-Langevin C, Merwin RM, Sachs DH, Asofsky R. Establishment and characterization of BALB/c lymphoma lines with B cell properties. J Immunol. 1979 Feb;122(2):549–554. [PubMed]
  • Braciale TJ, Andrew ME, Braciale VL. Heterogeneity and specificity of cloned lines of influenza-virus specific cytotoxic T lymphocytes. J Exp Med. 1981 Apr 1;153(4):910–923. [PMC free article] [PubMed]
  • Morrison LA, Lukacher AE, Braciale VL, Fan DP, Braciale TJ. Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med. 1986 Apr 1;163(4):903–921. [PMC free article] [PubMed]
  • Araneo BA, Woods ML, 2nd, Daynes RA. Reversal of the immunosenescent phenotype by dehydroepiandrosterone: hormone treatment provides an adjuvant effect on the immunization of aged mice with recombinant hepatitis B surface antigen. J Infect Dis. 1993 Apr;167(4):830–840. [PubMed]
  • Andrew ME, Braciale TJ. Antigen-dependent proliferation of cloned continuous lines of H-2-restricted influenza virus-specific cytotoxic T lymphocytes. J Immunol. 1981 Sep;127(3):1201–1204. [PubMed]
  • Gajewski TF, Lancki DW, Stack R, Fitch FW. "Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype. J Exp Med. 1994 Feb 1;179(2):481–491. [PMC free article] [PubMed]
  • Bevan MJ, Cohn M. Cytotoxic effects of antigen- and mitogen-induced T cells on various targets. J Immunol. 1975 Feb;114(2 Pt 1):559–565. [PubMed]
  • Ada GL, Jones PD. The immune response to influenza infection. Curr Top Microbiol Immunol. 1986;128:1–54. [PubMed]
  • Scherle PA, Gerhard W. Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J Exp Med. 1986 Oct 1;164(4):1114–1128. [PMC free article] [PubMed]
  • Bender BS, Croghan T, Zhang L, Small PA., Jr Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med. 1992 Apr 1;175(4):1143–1145. [PMC free article] [PubMed]
  • Scherle PA, Palladino G, Gerhard W. Mice can recover from pulmonary influenza virus infection in the absence of class I-restricted cytotoxic T cells. J Immunol. 1992 Jan 1;148(1):212–217. [PubMed]
  • Scalzo AA, Anders EM. Influenza viruses as lymphocyte mitogens. I. B cell mitogenesis by influenza A viruses of the H2 and H6 subtypes is controlled by the I-E/C subregion of the major histocompatibility complex. J Immunol. 1985 Feb;134(2):757–760. [PubMed]
  • Graham MB, Dalton DK, Giltinan D, Braciale VL, Stewart TA, Braciale TJ. Response to influenza infection in mice with a targeted disruption in the interferon gamma gene. J Exp Med. 1993 Nov 1;178(5):1725–1732. [PMC free article] [PubMed]
  • Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. [PubMed]
  • Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. [PMC free article] [PubMed]
  • Graham BS, Perkins MD, Wright PF, Karzon DT. Primary respiratory syncytial virus infection in mice. J Med Virol. 1988 Oct;26(2):153–162. [PubMed]
  • Carding SR, Allan W, McMickle A, Doherty PC. Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. J Exp Med. 1993 Feb 1;177(2):475–482. [PMC free article] [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...