Abstract
This study aimed to analyse the roles of Lyt 2+ and L3T4+ memory T-cell subpopulations in murine influenza infection. Previous work has shown that Lyt 2+ cytotoxic T-cell (Tc) clones can adoptively transfer protection. We therefore wished to see whether L3T4+ (Th) cells could also act as protective effector cells. Donors for adoptive cell transfer were thymectomized mice, depleted in vivo of either Lyt 2+ or L3T4+ T cells with monoclonal antibodies (MAb) and then infected with influenza virus (A/X31). Primed spleen cells, after removal of the B cells, were transferred into irradiated hosts infected simultaneously or persistently with a heterologous influenza virus and the effect on lung virus replication determined. Depletion of L3T4+ T cells suppressed the formation of IgG antibodies after influenza virus infection, indicating significant depletion of T-helper function. Yet Lyt 2+ class I MHC-restricted Tc cells were effectively primed in these mice, albeit to half the normal level. Adoptive transfer of the Lyt 2+ memory T cells cleared virus in a persistent infection within 6 days. Spleen cells selected for L3T4+ T cells cleared virus within 21 days of transfer in a simultaneous infection and reduced viral titres in a persistent infection, but not as effectively as L3T4+-depleted spleen cells. Although no Lyt 2+ cells were detected by fluorescence staining in Lyt 2+-depleted spleens, we could detect low levels of class I MHC-restricted influenza-specific Tc memory cells in host spleens following influenza infection. Therefore, whether the early viral clearance is solely due to L3T4+ T cells is not clear. Lyt 2+ memory T cells appear more efficient in this respect than L3T4+ memory T cells.
MeSH Terms
Animals
Antibodies, Viral/biosynthesis
Female
Immunization, Passive
Immunologic Memory
Influenza A virus/immunology
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections/immunology,prevention & control
T-Lymphocytes/classification
T-Lymphocytes, Cytotoxic/immunology
T-Lymphocytes, Helper-Inducer/immunology
Chemicals
Antibodies, Viral
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lightman S
Division of Immunology, National Institute for Medical Research, Mill Hill, London, U.K.
Cobbold S
Waldmann H
Askonas B A
References (24)
24 references, click to expand
-
Immunological unresponsiveness of genetically thymusless (nude) mice.
Eur J Immunol. 1971 Jan;1(1):59-61
PMID: 14978866
-
Serum immunoglobulin levels in nude mice.
Eur J Immunol. 1972 Oct;2(5):473-4
PMID: 4628494
-
Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses.
Nature. 1977 May 26;267(5609):354-6
PMID: 194164
-
Long term culture of tumour-specific cytotoxic T cells.
Nature. 1977 Jul 14;268(5616):154-6
PMID: 145543
-
Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells.
J Exp Med. 1978 Apr 1;147(4):1236-52
PMID: 306410
-
Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens.
Immunol Rev. 1979;47:63-90
PMID: 398327
-
Cross-protection and cross-reactive cytotoxic T cells induced by influenza virus vaccines in mice.
Eur J Immunol. 1980 May;10(5):396-401
PMID: 6967815
-
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):225-34
PMID: 6267157
-
MHC restriction of anti-viral immunity.
Immunol Rev. 1981;58:1-180
PMID: 7309039
-
Different functions of subsets of effector T cells in murine influenza virus infection.
Cell Immunol. 1982 Mar 1;67(2):312-24
PMID: 6979396
-
The recognition specificity of a murine helper T cell for hemagglutinin of influenza virus A/PR/8/34.
J Immunol. 1983 May;130(5):2379-85
PMID: 6187854
-
Recovery from a viral respiratory tract infection. IV. Specificity of protection by cytotoxic T lymphocytes.
J Immunol. 1983 Jun;130(6):2908-14
PMID: 6189904
-
Production of interleukin 2, interleukin 3, and interferon by mouse T lymphocyte clones of Lyt-2+ and -2- phenotype.
J Immunol. 1984 Apr;132(4):1869-71
PMID: 6199414
-
In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific.
J Exp Med. 1984 Sep 1;160(3):814-26
PMID: 6206190
-
Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo.
Nature. 1984 Dec 6-12;312(5994):548-51
PMID: 6150440
-
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):903-21
PMID: 3485173
-
Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences.
J Exp Med. 1986 Apr 1;163(4):998-1011
PMID: 3512763
-
Skin allograft rejection by L3/T4+ and Lyt-2+ T cell subsets.
Transplantation. 1986 May;41(5):634-9
PMID: 3085299
-
Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo.
Immunology. 1986 Jul;58(3):417-20
PMID: 2426185
-
Regulation of cytotoxic lymphocyte precursors. II. The effect of interleukin-2 and interferon-gamma on the apparent specificity of effector cells.
Cell Immunol. 1986 Jun;100(1):239-46
PMID: 3091261
-
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):1114-28
PMID: 2944982
-
IgG2a restriction of murine antibodies elicited by viral infections.
J Exp Med. 1987 Jan 1;165(1):64-9
PMID: 3794607
-
Different roles for L3T4+ and Lyt 2+ T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system.
J Gen Virol. 1987 Mar;68 ( Pt 3):825-33
PMID: 2950204
-
Functional analysis of T lymphocyte subsets in antiviral host defense.
J Immunol. 1987 Apr 1;138(7):2278-81
PMID: 2435794