Human Vdelta2+ gammadelta T-cell tolerance to foreign antigens of Toxoplasma gondii

Little is known about the mechanisms involved in human [Gamma][Delta] T-cell tolerance to self or to foreign antigens. Patients with congenital toxoplasmosis offer a unique opportunity to examine V[Delta][2.sup.+] [Gamma][Delta]d T-cell tolerance. Analysis of [Gamma][Delta] T cells in patients with congenital toxoplasmosis revealed evidence for anergy of these cells with or without clonal V[Delta][2.sup.+] [Gamma][Delta] 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 1 year of age, the repertoires of the [Gamma][Delta] T-cell receptors were found to be within normal ranges. In addition, in the chronic phase, the [Gamma][Delta] T cells proliferated and secreted [Gamma]-interferon in response to exposure to live Toxoplasma-infected cells. By contrast, [Alpha][Beta] T cells remained anergic. V[Delta][2.sup.+] [Gamma][Delta] T cells have been considered to undergo extrathymic maturation and thus to be subject to development of peripheral tolerance. Our findings indicate that V[Delta][2.sup.+] [Gamma][Delta] T-cell tolerance was lost in these infected infants earlier than [Alpha][Beta] T-cell tolerance. These findings suggest that [Gamma][Delta] 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 [Alpha][Beta] T cells continue to exhibit deficits in specific immune responses to Toxoplasma antigens.