Antigen-specific T cell responses in human peripheral blood leucocyte (hu-PBL)-mouse chimera conditioned with radiation and an antibody directed against the mouse IL-2 receptor beta-chain.
A weakness of the hu-PBL-SCID model for the study of human immune functions is the appearance of anergy and the consequent loss of T cell function. We demonstrate here that human T cells retain normal functions during the early stage of chimerism. At 1 and 2 weeks post-engraftment, T cells isolated from the peritoneal cavity of hu-PBL chimeras could be activated and proliferated upon stimulation with phytohaemagglutinin (PHA) or specific antigens to which the cell donor was known to be immune. T cells derived from hu-PBL-SCID and hu-PBL-NOD/LtSz-scid (NOD/SCID) mice not only proliferated but also produced interferon-gamma (IFN-gamma) and IL-5 following in vitro stimulation with tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg). These antigen-specific T cells could only be demonstrated when cognate antigen was administered together with or immediately following the PBL transfer. Without an early rechallenge with antigen in vivo, no TT- or HBsAg-specific T cell responses could be elicited, showing the vulnerability and antigen-dependence of the T cell response. Vigorous anti-TT or anti-HBs responses could be observed in all chimeras. Administration of antigen together with the PBL graft enhanced the humoral anti-TT response in SCID and NOD/SCID mice but had little effect on the anti-HBs antibody response in NOD/SCID mice. These data confirm the observation that the B cell compartment in hu-PBL-SCID chimera is largely antigen-independent and extend this to SCID/NOD.
Cao
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Centre for Vaccinology, Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, Belgium.
Leroux-Roels
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D000818:Animals; D017690:Cell Transplantation; D002678:Chimera; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D014916:Whole-Body Irradiation
D006514:Hepatitis B Surface Antigens; D015848:Interleukin-5; D015375:Receptors, Interleukin-2; D013745:Tetanus Toxoid; D007371:Interferon-gamma