Intrathymic activation events and the generation of IL-4 producer CD4+8- thymocytes.
The generation of mouse CD4+8- thymocytes appears to involve an activation process. CD69, an early activation marker, is first expressed on 3% of TCRlo/med double-positive thymocytes and peaks (70-90%) at the HSAhi TCRmed CD4+8lo and the HSAhi TCRhi CD4+8- stages, before being downmodulated. CD44, a marker of a later stage of activation is selectively expressed at the HSAlo CD4+8- stage. Functional changes associated with the late activated state, such as the transient acquisition of the potential to secrete IL-4 upon stimulation, are also induced at the HSAlo CD4+8- stage and are still evident after export to the periphery. During thymic selection, interactions of different affinities between TCR/CD4 and self ligand/MHC class II, are likely to induce different degrees of activation. This may impart different functional capabilities--such as the potential to secrete IL-4--to a subset of emerging CD4+ T lymphocytes that express TCRs with intermediate affinities for self. Such a pathway may be involved in the maintenance of tolerance and the prevention of some deleterious autoimmune reactions.
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
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Bendelac
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D015870:Gene Expression; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D013950:Thymus Gland / Q000166:cytology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D015847:Interleukin-4; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing; D000099192:CD69 Antigens