Impaired T cell functions preceding lymphoproliferative disorders in mice neonatally tolerized to transplantation antigens.
In A/J (H-2a) (A) mice, the neonatal i.v. injection of (B10 x A)F1 spleen cells (SC) induces partial transplantation tolerance (TT) to C57BL/10ScSn (H-2b) (B10) skin allografts, chronic host-versus-graft disease (HVGD) and lethal lymphoproliferative disorders (LPD). They produce anti-T-cell autoantibodies (ATA), and the proliferative responses of their SC to the T cell mitogen Con A are decreased. We found that, similar to ATA, the hyporeactivity of T cells developed earlier (at 1-2 weeks of age) than splenomegaly. The proportions of both CD4+ and CD8+ T cells were not reduced in the spleens of tolerized mice without manifest LPD. The supernatants (SN) of Con A-stimulated tolerized SC contained no, or only small amounts of interleukin-2 (IL-2). Thus, in the tolerized mice, ATA and T cell deficiency preceded the development of LPD. ATA and the decreased amount of the T cell growth factor IL-2 might play a role in the defective T cell activation.
Jánossy
T
T
Department of Experimental Surgery, Albert Szent-Györgyi Medical University, Hungary.
Vizler
C
C
Ocsovszki
I
I
Tibbe
G J
GJ
Pipis
J
J
Savelkoul
H F
HF
Végh
P
P
Benner
R
R
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D017690:Cell Transplantation; D002908:Chronic Disease; D003208:Concanavalin A / Q000494:pharmacology; D006789:Host vs Graft Reaction / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007376:Interleukin-2 / Q000032:analysis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count / Q000187:drug effects; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000494:pharmacology; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013163:Splenomegaly / Q000209:etiology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014181:Transplantation Immunology
D000941:Antigens; D001323:Autoantibodies; D007376:Interleukin-2; D008934:Mitogens; D003208:Concanavalin A