An age-related gamma delta T cell suppressor activity correlates with the outcome of autoimmunity in experimental Trypanosoma cruzi infection.
In this work the suppressive activity of splenic T cells from young and aged BALB/c mice infected with Trypanosoma cruzi were compared and correlated with the development of autoimmune myocarditis. The T cells from young adult BALB/c mice with acute T. cruzi infection exhibit suppressor activity when added to full allogeneic or Mls-disparate mixed lymphocyte cultures. This suppression could not be reverted by exogenous interleukin (IL)-2 and was not directly dependent on the presence of IL-4, IL-10 or transforming growth factor-beta. Further characterization of the T cell lineage responsible for the suppressor activity by in vitro and/or in vivo depletion with monoclonal antibody to alpha beta or gamma delta T cell receptor revealed that splenic gamma delta T cells function as suppressor lymphocytes in young T. cruzi-infected mice. In addition, these young adult BALB/c mice do not develop autoimmune myocarditis and showed a low incidence of syngeneic heart graft rejection in the early chronic phase of the infection. In contrast, T cells from acutely infected aged BALB/c mice lacked demonstrable T suppressor activity. Furthermore, these mice developed a severe autoimmune myocarditis as early as 2 months after the onset of the infection, when the majority of them reject syngeneic heart grafts. These findings suggest that a gamma delta T cell-mediated suppressor mechanism may operate in the avoidance of the breaking of tissue-specific tolerance during the acute infection. Moreover, such a mechanism is likely related to the immune system chronobiology.
Cardillo
F
F
Department of Immunology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
Falcão
R P
RP
Rossi
M A
MA
Mengel
J
J
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D015551:Autoimmunity; D001667:Binding, Competitive; D002448:Cell Adhesion; D002598:Chagas Cardiomyopathy / Q000209:etiology / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma