Ig-specific T cell receptor-transgenic T cells are not deleted in the thymus and are functional in vivo.
The mechanisms that induce T cell tolerance to circulating self-proteins are still controversial, and both the deletion and selection of autoreactive T cells have been observed in the thymus of transgenic mouse models. To address the question of the induction of tolerance to circulating self-constituents, a T cell receptor-transgenic mouse specific for the serum protein immunoglobulin (Ig) gamma and (IgG2ab) was generated. The choice of an allotype-specific T cell also allowed the generation of transgenic control mice not expressing the self-antigen. It was found that the transgenic T cells were not deleted in the thymus, did not become tolerant in the periphery, and regulated the function of gamma 2ab-positive B cells as shown by the lack of IgG2ab protein in the serum of the transgenic mice. In spite of this activity in vivo, the transgenic T cells did not proliferate in vitro in response to the allotype-specific peptide. Interestingly, antigen-specific T cell proliferation could be restored if the transgenic mice were previously challenged to induce IgG2ab responses. After this challenge, IgG2ab protein in the serum of the transgenic mice could be partially restored, although still remaining much lower than in control mice. In addition, there was a dramatic increase in serum IgE levels, suggesting that newly generated gamma 2ab-secreting B cells can be induced to switch to IgE in the presence of allotype-specific T cells. These results indicate that Ig-specific T cells may represent a late-acting form of T cell help for the regulation of the IgG2a-to-IgE class switch.
Granucci
F
F
Italian National Research Council, Centre of Cytopharmacology, Milan, Italy.
Rescigno
M
M
Marconi
G
G
Foti
M
M
Ricciardi-Castagnoli
P
P
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D005434:Flow Cytometry; D007108:Immune Tolerance; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000032:analysis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013934:Thymectomy; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000601:surgery
D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D017452:Receptors, IgG