Antigen-specific CD4+ T cells that survive after the induction of peripheral tolerance possess an intrinsic lymphokine production defect.
Injection of soluble foreign antigen without an adjuvant induces a state of antigen-specific immunological unresponsiveness. We investigated the cellular mechanisms that underlie this form of peripheral tolerance by physically tracking a small population of ovalbumin (OVA) peptide/I-Ad-specific, CD4+ T cell receptor (TCR) transgenic T cells following adoptive transfer into normal recipients. Injection of OVA peptide in the absence of adjuvant caused the antigen-specific T cells to proliferate for a brief period after which most of the T cells disappeared. The remaining OVA-specific T cells had converted to a memory phenotype but were poorly responsive in vivo as evidenced by a failure to accumulate in the draining lymph nodes following immunization with OVA peptide in adjuvant. These surviving T cells possessed a long-lasting, but reversible, defect in Il-2 and TNF-alpha production and in vivo proliferation, but did not gain capacity to produce Th2-type cytokines or suppress the clonal expansion of T cells specific for another antigen. Therefore, some antigen-specific T cells survive this peripheral tolerance protocol but are functionally unresponsive due to an intrinsic activation defect.
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455, USA.
K A
KA
Pape
A
A
Khoruts
E
E
Ingulli
A
A
Mondino
R
R
Merica
M K
MK
Jenkins
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis*; D018448:Models, Immunological; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007376:Interleukin-2; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin