The development of functionally responsive T cells - PubMed (original) (raw)
Review
The development of functionally responsive T cells
E V Rothenberg. Adv Immunol. 1992.
Abstract
The work reviewed in this article separates T cell development into four phases. First is an expansion phase prior to TCR rearrangement, which appears to be correlated with programming of at least some response genes for inducibility. This phase can occur to some extent outside of the thymus. However, the profound T cell deficit of nude mice indicates that the thymus is by far the most potent site for inducing the expansion per se, even if other sites can induce some response acquisition. Second is a controlled phase of TCR gene rearrangement. The details of the regulatory mechanism that selects particular loci for rearrangement are still not known. It seems that the rearrangement of the TCR gamma loci in the gamma delta lineage may not always take place at a developmental stage strictly equivalent to the rearrangement of TCR beta in the alpha beta lineage, and it is not clear just how early the two lineages diverge. In the TCR alpha beta lineage, however, the final gene rearrangement events are accompanied by rapid proliferation and an interruption in cellular response gene inducibility. The loss of conventional responsiveness is probably caused by alterations at the level of signaling, and may be a manifestation of the physiological state that is a precondition for selection. Third is the complex process of selection. Whereas peripheral T cells can undergo forms of positive selection (by antigen-driven clonal expansion) and negative selection (by abortive stimulation leading to anergy or death), neither is exactly the same phenomenon that occurs in the thymic cortex. Negative selection in the cortex appears to be a suicidal inversion of antigen responsiveness: instead of turning on IL-2 expression, the activated cell destroys its own chromatin. The genes that need to be induced for this response are not yet identified, but it is unquestionably a form of activation. It is interesting that in humans and rats, cortical thymocytes undergoing negative selection can still induce IL-2R alpha expression and even be rescued in vitro, if exogenous IL-2 is provided. Perhaps murine thymocytes are denied this form of rescue because they shut off IL-2R beta chain expression at an earlier stage or because they may be uncommonly Bcl-2 deficient (cf. Sentman et al., 1991; Strasser et al., 1991). Even so, medullary thymocytes remain at least partially susceptible to negative selection even as they continue to mature.(ABSTRACT TRUNCATED AT 400 WORDS)
Similar articles
- In vitro expansion of CD3/TCR- human thymocyte populations that selectively lack CD3 delta gene expression: a phenotypic and functional analysis.
Poggi A, Biassoni R, Pella N, Paolieri F, Bellomo R, Bertolini A, Moretta L, Mingari MC. Poggi A, et al. J Exp Med. 1990 Nov 1;172(5):1409-18. doi: 10.1084/jem.172.5.1409. J Exp Med. 1990. PMID: 2146363 Free PMC article. - Repertoire development and ligand specificity of murine TCR gamma delta cells.
Bluestone JA, Cron RQ, Barrett TA, Houlden B, Sperling AI, Dent A, Hedrick S, Rellahan B, Matis LA. Bluestone JA, et al. Immunol Rev. 1991 Apr;120:5-33. doi: 10.1111/j.1600-065x.1991.tb00585.x. Immunol Rev. 1991. PMID: 1650760 Review. - Fc gamma RII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8- murine thymocytes: in vivo developmental kinetics and T cell receptor beta chain rearrangement status.
Rodewald HR, Awad K, Moingeon P, D'Adamio L, Rabinowitz D, Shinkai Y, Alt FW, Reinherz EL. Rodewald HR, et al. J Exp Med. 1993 Apr 1;177(4):1079-92. doi: 10.1084/jem.177.4.1079. J Exp Med. 1993. PMID: 8096236 Free PMC article. - A novel role for HEB downstream or parallel to the pre-TCR signaling pathway during alpha beta thymopoiesis.
Barndt R, Dai MF, Zhuang Y. Barndt R, et al. J Immunol. 1999 Sep 15;163(6):3331-43. J Immunol. 1999. PMID: 10477603 - Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.
Coutinho A, Caramalho I, Seixas E, Demengeot J. Coutinho A, et al. Curr Top Microbiol Immunol. 2005;293:43-71. doi: 10.1007/3-540-27702-1_3. Curr Top Microbiol Immunol. 2005. PMID: 15981475 Review.
Cited by
- Immunological considerations in in utero hematopoetic stem cell transplantation (IUHCT).
Loewendorf AI, Csete M, Flake A. Loewendorf AI, et al. Front Pharmacol. 2015 Jan 6;5:282. doi: 10.3389/fphar.2014.00282. eCollection 2014. Front Pharmacol. 2015. PMID: 25610396 Free PMC article. Review. - CDK6 kinase activity is required for thymocyte development.
Hu MG, Deshpande A, Schlichting N, Hinds EA, Mao C, Dose M, Hu GF, Van Etten RA, Gounari F, Hinds PW. Hu MG, et al. Blood. 2011 Jun 9;117(23):6120-31. doi: 10.1182/blood-2010-08-300517. Epub 2011 Apr 20. Blood. 2011. PMID: 21508411 Free PMC article. - BONE MARROW, THYMUS AND BLOOD: CHANGES ACROSS THE LIFESPAN.
[No authors listed] [No authors listed] Aging health. 2009 Jun 1;5(3):385-393. doi: 10.2217/ahe.09.31. Aging health. 2009. PMID: 20072723 Free PMC article. - Psychological stress as a factor potentially contributing to the pathogenesis of Type 1 diabetes mellitus.
Karavanaki K, Tsoka E, Liacopoulou M, Karayianni C, Petrou V, Pippidou E, Brisimitzi M, Mavrikiou M, Kakleas K, Dacou-Voutetakis C. Karavanaki K, et al. J Endocrinol Invest. 2008 May;31(5):406-15. doi: 10.1007/BF03346384. J Endocrinol Invest. 2008. PMID: 18560258 - Progression of regulatory gene expression states in fetal and adult pro-T-cell development.
David-Fung ES, Yui MA, Morales M, Wang H, Taghon T, Diamond RA, Rothenberg EV. David-Fung ES, et al. Immunol Rev. 2006 Feb;209:212-36. doi: 10.1111/j.0105-2896.2006.00355.x. Immunol Rev. 2006. PMID: 16448545 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources