Characterization of host CD4+ T lymphocytes in mice neonatally tolerized to alloantigens.
BALB/c mice injected at birth with semi-allogeneic F1 spleen cells become tolerant to alloantigens as shown by their CTL unresponsiveness to the corresponding alloantigen and the persistence of donor F1 cells into the BALB/c host. Moreover, these mice develop a transient systemic lupus erythematosis-like autoimmune syndrome characterized by splenomegaly, glomerulonephritis, thrombocytopenia and abnormal serological findings, such as several autoantibodies and IgG1 hypergammaglobulinemia. Recent studies done in our laboratory have shown that donor F1 B cells persisting in the host are responsible for the production of autoantibodies and must be activated in vivo by the host CD4+ T lymphocytes in a MHC class II-restricted fashion. In the present work, we have focused our attention on the ability of splenic CD4+ T cells recovered at different periods from BALB/c mice injected at birth with (CBA/Ca x BALB.Ighb) F1 spleen cells to interact with and activate F1 semi-allogeneic spleen cells in vitro. We show that (i) only CD4+ T cells from 2- and 3-week-old tolerant BALB/c mice preferentially produce IL-4 and IL-5 in response to a F1 semi-allogeneic in vitro stimulation, (ii) CD4+ T cells purified from 3-week-old tolerant BALB/c mice are able to induce in vitro IgG and IgM production by F1 B cells. Taken together, these results strongly suggest that host CD4+ T cells, belonging to the TH2 subset progressively lose their reactivity towards the F1 semi-allogeneic persistent B cells, reaching a state of unresponsiveness that correlates with the disappearance of serum autoantibodies and autoimmune pathology.
Kramar
G
G
World Health Organization-Immunology Research and Training Center, Department of Pathology, Geneva, Switzerland.
Aguado
T
T
Louis
J
J
del Giudice
G
G
Lambert
P H
PH
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007519:Isoantigens / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; D017931:DNA Primers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015848:Interleukin-5; D007519:Isoantigens; D015847:Interleukin-4