Identification and characterization of protective T cells in hsp65 DNA-vaccinated and Mycobacterium tuberculosis-infected mice.
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.
Bonato
V L
VL
Department of Parasitology, Microbiology and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Lima
V M
VM
Tascon
R E
RE
Lowrie
D B
DB
Silva
C L
CL
D019264:Adoptive Transfer; D000818:Animals; D001426:Bacterial Proteins; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D001426:Bacterial Proteins; D015704:CD4 Antigens; D016827:CD8 Antigens; D018834:Chaperonin 60; D018960:Hyaluronan Receptors; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D015847:Interleukin-4; D007371:Interferon-gamma; D018833:Chaperonins