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.
Bendelac
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Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
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