Contribution of extrathymic gamma delta T cells to the expression of heat-shock protein and to protective immunity in mice infected with Toxoplasma gondii.
We demonstrated that gamma delta T cells contribute to protective immunity against Toxoplasma gondii by inducing the expression of a 65,000 MW heat-shock protein (hsp 65) in host macrophages. Here we examined the role of extrathymic and intrathymic gamma delta T cells in protective immunity and hsp 65 expression in mice infected with T. gondii. Intrathymic gamma delta T cells were obtained from severe combined immunodeficiency (SCID) mice grafted with syngeneic fetal thymus (TG-SCID), in which only T cells derived from the donor thymus developed, whereas extrathymic gamma delta T cells were obtained from nude mice that lack thymus. Extrathymic gamma delta T cells from T. gondii-infected nude mice differed from intrathymic gamma delta T cells of infected TG-SCID mice, in terms of Thy1.2 expression and V-region gene usage of T-cell receptor (TCR) gamma delta. Extrathymic gamma delta T cells expressed extremely high levels of Thy1.2, and had V gamma 7 repertoire but lacked V gamma 5,6 and V delta 1,5. On the other hand, intrathymic gamma delta T cells express intermediate and low levels of Thy1,2. These cells possessed V gamma 5,6 and V delta 1,5 but failed to rearrange the V gamma 7 gene. Peritoneal macrophages from infected nude mice contained hsp 65, whereas this protein was scarcely expressed in those of infected TG-SCID mice. Transfer of extrathymic, but not of intrathymic gamma delta T cells to SCID mice enabled their macrophages to express hsp 65. Athymic nude mice were significantly resistant to the infection compared with SCID mice which lack gamma delta T as well as alpha beta T cells. The resistance was dependent upon extrathymic gamma delta T cells, since nude mice depleted of gamma delta T cells using a corresponding monoclonal antibody became extremely susceptible. These results indicated that extrathymic rather than intrathymic gamma delta T cells play some crucial roles in protection against T. gondii and in hsp 65 expression.
Hisaeda
H
H
Department of Parasitology and Immunology, University of Tokushima, Japan.
Sakai
T
T
Nagasawa
H
H
Ishikawa
H
H
Yasutomo
K
K
Maekawa
Y
Y
Himeno
K
K
D000818:Animals; D001426:Bacterial Proteins; D001483:Base Sequence; D015153:Blotting, Western; D018834:Chaperonin 60; D018833:Chaperonins / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D001426:Bacterial Proteins; D018834:Chaperonin 60; D016692:Receptors, Antigen, T-Cell, gamma-delta; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins