Thymic Shared Antigen-2: A Novel Cell Surface Marker Associated with T Cell Differentiation and Activation1 (original) (raw)
Related papers
1999
Thymic shared Ag-2 (TSA-2) is a 28-kDa, glycophosphatidylinitosol-linked cell surface molecule expressed on various T cell and thymic stromal cell subsets. It is expressed on most CD3-CD4-CD8-, CD4+CD8+, and CD3highCD4-CD8+ thymocytes but is down-regulated on approximately 40% of CD3highCD4+CD8- thymocytes. Expression on peripheral TCR-alphabeta+ T cells is similar to that of CD3+ thymocytes, although a transient down-regulation occurs with cell activation. Consistent with the recent hypothesis that emigration from the thymus is an active process, recent thymic emigrants are primarily TSA-2-/low. TSA-2 expression reveals heterogeneity among subpopulations of CD3highCD4+CD8- thymocytes and TCR-gamma delta+ T cell previously regarded as homogenous. The functional importance of TSA-2 was illustrated by the severe block in T cell differentiation caused by adding purified anti-TSA-2 mAb to reconstituted fetal thymic organ culture. While each CD25/CD44-defined triple-negative subset was p...
Proceedings of the National Academy of Sciences, 1986
In vivo, immunocompetent T lymphocytes are only detected late in ontogeny, among mature thymocytes expressing either T4 (L3T4 in mouse) or T8 (Lyt-2) surface glycoproteins. We have previously shown, however, that there are functional precursors among T3+4-6-8human thymocytes in vivo. Here we report on the in vitro differentiation of prothymocytes into T3+4-6-8and mature T cells. T11+3-4-6-8prothymocytes (0.5% of total thymocytes, >98% pure) were obtained after treatment of thymocytes with OKT3 (T3), OKT4A (T4), Nal/34 (T6), and B9.4 (T8) monoclonal antibodies plus complement. During culture, the prothymocyte precursors acquire first T3 and then either T4 or T8, but not T6. The largest subpopulation in the thymus, T4+6+8+ cells, are not detected among the in vitro T-cell precursors. During culture, the precursors acquire cytolytic activity as soon as they express either the T3+4-6-8or the mature (T3+4+8or T3+4-8+) phenotypes. We suggest that T3+4-6-8cells are a productive, transitional stage in T-lymphocyte development.
Responsiveness of fetal and adult CD4-, CD8- thymocytes to T cell activation
The Journal of Immunology
Day-14 fetal CD4-, CD8- thymocytes showed a greater proliferative response to PMA + IL-4 than did adult double-negative thymocytes. In contrast, adult double-negative thymocytes were more responsive to PMA + IL-1 + IL-2 or to IL-1 + IL-2 alone. The adult double-negative thymocytes showed significantly greater proliferation than fetal thymocytes after stimulation via anti-CD3 or anti-Thy-1 in the presence or absence of interleukins (IL-1 + IL-2 or IL-4). Adult CD4-, CD8- thymocytes also exhibited greater calcium mobilization following anti-CD3 stimulation IL-2-dependent activation with anti-Thy-1 or IL-1 + IL-2 in the absence of PMA resulted in marked expansion of CD 3+, F23.1+, CD4-, CD8- thymocytes, a population absent in fetal thymocytes but constituting 4% of pre-cultured CD4-, CD8- adult thymocytes. IL-4 + PMA failed to expand this CD 3+ population. It is hypothesized that before expression of functional TCR, T cell development may be more dependent on activation pathways not us...
A Molecular Map of T Cell Development
Immunity, 1998
; Fehling and von Boehmer, 1997). Early * Section of Immunology stages of thymocyte development are clearly defined Yale University School of Medicine by several molecular events that include expression of Howard Hughes Medical Institute the RAG-1 and RAG-2 gene products (Lin and Desiderio, New Haven, Connecticut 06520-8011 1993; Ferguson et al., 1994; Hoffman et al., 1996), so-† Laboratory of Immunology matic rearrangement of the T cell receptor  chain locus, National Institute of Allergy and Infectious Diseases expression of the coreceptor molecules CD4 and CD8, National Institutes of Health and, finally, recombination of the TCR ␣ locus (Dudley Bethesda, Maryland 20892 et al., 1994; Petrie et al., 1995). Productive rearrange-‡ Department of Molecular Biotechnology ment of both TCR chains allows surface expression of University of Washington School of Medicine the TCR and ensures life up to this point. Further devel-Seattle, Washington 98195-7650 opment, however, relies in part (Tourigny et al., 1997) upon signals generated by TCR interaction with MHC: self peptide complexes (von Boehmer, 1994). Most thy-Summary mocytes fail this rigorous criterion for selection and die of neglect (Janeway, 1994). Using a sensitive molecular marker for positive selec-While the early events in development can be clearly tion, the appearance of a particular functional TCR ␣ defined by molecular events, later stages of developchain sequence in cells from mice bearing a transgenic ment are typically defined by variations in the expression levels of cell surface proteins such as CD4, CD8, and  chain, we address several aspects of intrathymic T the TCR. These molecules allow for several different cell development. First, by examining specific TCR intrathymic subpopulations to be distinguished. The deprior to and after maturation, we demonstrate how a velopmental status of such populations has been, in restricted TCR repertoire is positively selected from most cases, assessed by other means including intraa highly diverse immature TCR repertoire. Second, thymic injections of genetically marked cells and reconsince this molecular marker is enriched in cells prostitution of thymocytes in irradiated mice. gressing toward the CD4 lineage and depleted in cells In this report, we identify a sensitive molecular marker progressing toward the CD8 lineage, a map of the for positive selection. This marker, which is the appeardevelopmental pathway of ␣ thymocytes can be inance or loss of a specific TCR ␣ chain sequence, is used ferred. Third, the first cells that show clear signs of to address three issues concerning the development of positive intrathymic selection are identified. TCR␣ bearing thymocytes. First, we demonstrate that the restriction of TCR usage that was apparent in the mature repertoire in "single-peptide" mice bearing a Peptide-Specific Responses of Nonimmunized TCR  Chain Transgenic Thymocytes § To whom correspondence should be addressed (e-mail: derek.
Cellular Immunology, 1991
We have recently demonstrated that bone marrow-resident cells, which are able to repopulate the thymus of irradiated recipient mice (pre-T cells), can be maintained in vitro for at least 2 weeks in the presence of exogenous IL-3. Because this marrow culture system can be applied to the study of early T cell differentiation, it is important to ascertain the extent to which in vitro culture of the pre-T cells might alter the T cell progeny which can develop from them. In previous work, we showed that the progeny of cultured pre-T cells appeared to develop in a kinetically normal fashion within the thymus of recipients and that the acquisition of key developmental markers (IL-2R and CD3) was identical in the progeny of fresh and cultured pre-T cells. Here, we report the results of experiments carried out to characterize the progeny of cultured pre-T cells which were found in the peripheral lymphoid tissues several weeks following intrathymic transfer to irradiated recipients. We found no remarkable differences between the progeny of cultured or fresh marrow cells with respect to the timing of their appearance in the periphery nor their expression of CD4 or CD8. By studying the patterns of utilization of five different VP gene products by the T cells derived from fresh or cultured bone marrow, we were able to test the susceptibility of both sets of progeny to both positive and negative selection pressures during their in vivo maturation. These experiments established that the progeny of cultured marrow cells were equally susceptible to TCR repertoire selection, as were the progeny of fresh bone marrow cells, and that the process of in vitro growth did not alter the potential TCR repertoire of the pre-T CdS.
Post-thymic maturation: young T cells assert their individuality
Nature Reviews Immunology, 2011
T cell maturation was once thought to occur entirely within the thymus. Now, evidence is mounting that the youngest peripheral T cells in both mice and humans comprise a distinct population from their more mature, yet still naive, counterparts. These cells, termed recent thymic emigrants (RTEs), undergo a process of post-thymic maturation that can be monitored at the levels of cell phenotype and immune function. Understanding this final maturation step in the process of generating useful and safe T cells is of clinical relevance, given that RTEs are over-represented in neonates and in adults recovering from lymphopenia. Post-thymic maturation may function to ensure T cell fitness and self tolerance.