Human V delta 2+ gamma delta T-cell tolerance to foreign antigens of Toxoplasma gondii.
Little is known about the mechanisms involved in human gammadelta T-cell tolerance to self or to foreign antigens. Patients with congenital toxoplasmosis offer a unique opportunity to examine Vdelta2+ gammadelta T-cell tolerance. Analysis of gammadelta T cells in patients with congenital toxoplasmosis revealed evidence for anergy of these cells with or without clonal Vdelta2+ gammadelta T-cell expansion in the acute phase of the Toxoplasma infection. T cells in general were unresponsive and did not proliferate upon exposure to mitogens or to Toxoplasma lysate antigens or in response to live Toxoplasma-infected cells when the congenitally infected infants were 1 month of age, and they exhibited selective anergy to Toxoplasma lysate antigens and live Toxoplasma-infected cells when the infants were aged 5 months. During the chronic phase of congenital toxoplasmosis in the patients who were more than I year of age, the repertoires of the gammadelta T-cell receptors were found to be within normal ranges. In addition, in the chronic phase, the gammadelta T cells proliferated and secreted gamma-interferon in response to exposure to live Toxoplasmia-infected cells. By contrast, alphabeta T cells remained anergic. Vdelta2+ gammadelta T cells have been considered to undergo extrathymic maturation and thus to be subject to development of peripheral tolerance. Our findings indicate that Vdelta2+ gammadelta T-cell tolerance was lost in these infected infants earlier than alphabeta T-cell tolerance. These findings suggest that gammadelta T cells play a role in protection against Toxoplasma gondii in the chronic phase when congenitally infected children are more than 1 year of age, especially in those in whom alphabeta T cells continue to exhibit deficits in specific immune responses to Toxoplasma antigens.
Hara
T
T
Department of Child Neurology, Institute of Neurological Sciences, Tottori University School of Medicine, Japan.
Ohashi
S
S
Yamashita
Y
Y
Abe
T
T
Hisaeda
H
H
Himeno
K
K
Good
R A
RA
Takeshita
K
K
D000208:Acute Disease; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014125:Toxoplasmosis, Congenital / Q000276:immunology
D000953:Antigens, Protozoan; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma