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PMID: 9423854 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification and characterization of protective T cells in hsp65 DNA-vaccinated and Mycobacterium tuberculosis-infected mice.

Infection and immunity ·Vol. 66 ·No. 1 ·1998-01-00 ·Pages 169-75

Bonato VL, Lima VM, Tascon RE, Lowrie DB, Silva CL

Abstract

Immunization by intramuscular injection of plasmid DNA expressing mycobacterial 65-kDa heat shock protein (hsp65) protects mice against challenge with virulent Mycobacterium tuberculosis H37Rv. During infection or after immunization, CD4+/CD8- and CD8+/CD4- hsp65-reactive T cells increased equally in spleens. During infection, the majority of these cells were weakly CD44 positive (CD44(lo)) and produced interleukin 4 (IL-4) whereas after immunization the majority were highly CD44 positive (CD44(hi)) and produced gamma interferon (IFN-gamma). In adoptive transfer of protection to naive mice, the total CD8+/CD4- cell population purified from spleens of immunized mice was more protective than that from infected mice. When the cells were separated into CD4+/CD8- and CD8+/CD4- types and then into CD44(hi) and CD44(lo) types, CD44(lo) cells were essentially unable to transfer protection, the most protective CD44(hi) cells were CD8+/CD4-, and those from immunized mice were much more protective than those from infected mice. Thus, whereas the CD44(lo) IL-4-producing phenotype prevailed during infection, protection was associated with the CD8+/CD44(hi) IFN-gamma-producing phenotype that predominated after immunization. This conclusion was confirmed and extended by analysis of 16 hsp65-reactive T-cell clones from infected mice and 16 from immunized mice; the most protective clones, in addition, displayed antigen-specific cytotoxicity.

MeSH Terms
Adoptive Transfer Animals Bacterial Proteins CD4 Antigens/immunology,metabolism CD8 Antigens/immunology,metabolism Chaperonin 60 Chaperonins/genetics,immunology Clone Cells/immunology Flow Cytometry Hyaluronan Receptors/immunology,metabolism Interferon-gamma/metabolism Interleukin-4/metabolism Mice Mice, Inbred BALB C Mycobacterium tuberculosis/immunology Spleen/cytology,immunology T-Lymphocyte Subsets/immunology Tuberculosis/immunology,prevention & control Vaccination Vaccines, DNA/immunology
Chemicals
Bacterial Proteins CD4 Antigens CD8 Antigens Chaperonin 60 Hyaluronan Receptors Vaccines, DNA heat-shock protein 65, Mycobacterium Interleukin-4 Interferon-gamma Chaperonins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bonato V L
Department of Parasitology, Microbiology and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Lima V M
Tascon R E
Lowrie D B
Silva C L
References (39)
39 references, click to expand
  1. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation.
    Cell. 1994 Jan 28;76(2):287-99 PMID: 8293464
  2. Differential effects of IL-10 on proliferation and cytokine production of human gamma/delta and alpha/beta T cells.
    Scand J Immunol. 1994 Feb;39(2):209-15 PMID: 8296165
  3. A single mycobacterial protein (hsp 65) expressed by a transgenic antigen-presenting cell vaccinates mice against tuberculosis.
    Immunology. 1994 Jun;82(2):244-8 PMID: 7927495
  4. Role of T cell subsets in immunity against intracellular bacteria: experimental infections of knock-out mice with Listeria monocytogenes and Mycobacterium bovis BCG.
    Immunobiology. 1994 Oct;191(4-5):509-19 PMID: 7713565
  5. Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis.
    J Clin Invest. 1995 Jul;96(1):245-9 PMID: 7615794
  6. T-cell cytokine responses in human infection with Mycobacterium tuberculosis.
    Infect Immun. 1995 Aug;63(8):3231-4 PMID: 7622255
  7. Role of interferon-gamma in immune cell regulation.
    J Leukoc Biol. 1995 Oct;58(4):373-81 PMID: 7561512
  8. Growth hormone activation of human monocytes for superoxide production but not tumor necrosis factor production, cell adherence, or action against Mycobacterium tuberculosis.
    Infect Immun. 1995 Nov;63(11):4312-6 PMID: 7591064
  9. Protective role of gamma/delta T cells and alpha/beta T cells in tuberculosis.
    Eur J Immunol. 1995 Oct;25(10):2877-81 PMID: 7589086
  10. Immunity to intracellular microbial pathogens.
    Immunol Today. 1995 Jul;16(7):338-42 PMID: 7576070
  11. Sequential production of Th1 and Th2 cytokines in response to live bacillus Calmette-Guérin.
    Immunology. 1995 Dec;86(4):512-8 PMID: 8567014
  12. Protection against tuberculosis by bone marrow cells expressing mycobacterial hsp65.
    Immunology. 1995 Dec;86(4):519-24 PMID: 8567015
  13. Characterization of T cells that confer a high degree of protective immunity against tuberculosis in mice after vaccination with tumor cells expressing mycobacterial hsp65.
    Infect Immun. 1996 Jul;64(7):2400-7 PMID: 8698458
  14. Vaccination against tuberculosis by DNA injection.
    Nat Med. 1996 Aug;2(8):888-92 PMID: 8705858
  15. The regulation of the development of CD8 effector T cells.
    J Immunol. 1996 Nov 15;157(10):4287-92 PMID: 8906801
  16. Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis.
    Immunology. 1996 Sep;89(1):26-33 PMID: 8911136
  17. Apparent killing of Mycobacterium tuberculosis by cytokine-activated human monocytes can be an artefact of a cytotoxic effect on the monocytes.
    Clin Exp Immunol. 1994 May;96(2):214-7 PMID: 8187329
  18. Acquisition of lymphokine-producing phenotype by CD4+ T cells.
    Annu Rev Immunol. 1994;12:635-73 PMID: 7912089
  19. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay.
    J Exp Med. 1976 May 1;143(5):1283-8 PMID: 1083422
  20. Natural killer cells and interferon.
    Crit Rev Immunol. 1984;5(1):55-93 PMID: 6085941
  21. Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64-kDa protein.
    Eur J Immunol. 1987 Mar;17(3):351-7 PMID: 3106059
  22. Phenotypic and functional analysis of murine CD3+,CD4-,CD8- TCR-gamma delta-expressing peripheral T cells.
    J Immunol. 1989 Jun 1;142(11):3754-62 PMID: 2523934
  23. CD8+ T lymphocytes in intracellular microbial infections.
    Immunol Today. 1988 Jun;9(6):168-74 PMID: 3151440
  24. A ubiquitous mammalian expression vector, pHMG, based on a housekeeping gene promoter.
    Nucleic Acids Res. 1989 Oct 25;17(20):8389 PMID: 2813075
  25. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens.
    J Immunol. 1992 Jan 1;148(1):189-96 PMID: 1727865
  26. Mycobacterium leprae 65hsp antigen expressed from a retroviral vector in a macrophage cell line is presented to T cells in association with MHC class II in addition to MHC class I.
    Microb Pathog. 1992 Jan;12(1):27-38 PMID: 1560752
  27. Parallel regulation of IL-4 and IL-5 in human helminth infections.
    J Immunol. 1992 Jun 1;148(11):3567-71 PMID: 1350292
  28. Cytokine patterns of immunologically mediated tissue damage.
    J Immunol. 1992 Aug 15;149(4):1470-5 PMID: 1500726
  29. Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells.
    J Exp Med. 1992 Aug 1;176(2):581-6 PMID: 1354243
  30. Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection.
    J Immunol. 1993 Jul 1;151(1):518-25 PMID: 8100846
  31. The age-associated increase in IFN-gamma synthesis by mouse CD8+ T cells correlates with shifts in the frequencies of cell subsets defined by membrane CD44, CD45RB, 3G11, and MEL-14 expression.
    J Immunol. 1993 Jul 15;151(2):575-87 PMID: 7687616
  32. Immunoregulatory effects of cytokines on natural killer cells.
    Scand J Immunol. 1994 Aug;40(2):128-34 PMID: 8047834
  33. Major histocompatibility complex class I-restricted T cells are necessary for protection against M. tuberculosis in mice.
    Infect Agents Dis. 1993 Aug;2(4):259-62 PMID: 8173805
  34. Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guérin.
    J Exp Med. 1994 Oct 1;180(4):1499-509 PMID: 7931080
  35. Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles.
    J Exp Med. 1994 Nov 1;180(5):1715-28 PMID: 7525836
  36. The functional role of CD8+ T helper type 2 cells.
    J Exp Med. 1995 Jan 1;181(1):5-7 PMID: 7807025
  37. The role of TNF-alpha in T-cell-mediated inflammation depends on the Th1/Th2 cytokine balance.
    Immunology. 1994 Aug;82(4):591-5 PMID: 7835922
  38. Protection against tuberculosis by passive transfer with T-cell clones recognizing mycobacterial heat-shock protein 65.
    Immunology. 1994 Nov;83(3):341-6 PMID: 7835957
  39. Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokines.
    Immunity. 1995 Mar;2(3):271-9 PMID: 7697544
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.66.1.169-175.1998
Published
1998-01-00
Pages
169-75
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC107873
Subset
IM
External Links
PubMed source DOI: 10.1128/IAI.66.1.169-175.1998 PMC Full Text View journal details
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