Induction of graft versus host-associated immunodeficiency by CD4+ T cell clones.
Previous studies have shown that the injection of parental T cells into MHC class II mismatched F1 recipient mice can lead to graft-vs-host (GvH) reaction that manifests itself by multiple symptoms. The objective of our study was to analyze GvH reactivity induced by a single T cell clone specific for host I-A or I-E alloantigen. The T cell clones tested for GvH potential were CD4+, with or without cytolytic activity in vitro and with a lymphokine pattern that classifies them as Th1 cells. The inoculation of a single T cell clone induced a severe, but transient immunodeficiency in the host that was independent of its cytolytic activity, as demonstrated by the failure to generate a CTL response to third party allogeneic cells in vitro. Induction of immunodeficiency in the recipients required preactivation of the clones in vitro by rIl-2 and the presence of the stimulator class II alloantigen in the host. Spleen cells from these mice lacked suppressor cells, they were deficient in Il-2 secretion and exhibited a decrease in the number of CD4+ T cells. In addition, I-E expression was reduced, however, without any changes in the macrophage population and an increase in surface Ig and the B cell marker B220. Simultaneous to the immunodeficiency, the clone-injected mice produced elevated antibody titers to ssDNA.
Tary-Lehmann
M
M
Preclinical Research, Sandoz, Ltd., Basel, Switzerland.
Rolink
A G
AG
Lehmann
P V
PV
Nagy
Z A
ZA
Hurtenbach
U
U
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006087:Graft vs Host Reaction / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
D000954:Antigens, Surface; D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II