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Differentiation to T helper cells in the thymus : gradual acquisition of T helper cell function by CD3⁺CD4⁺ cells

(1995) JOURNAL OF IMMUNOLOGY. 155(10). p.4711-4718
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Abstract
We investigated at which point during thymocyte differentiation functions were acquired that are characteristic for mature Th cells. Differentiation from CD3(+)CD69(-), CD4(+)CD8(+) double-positive (DP) cells to terminally differentiated CD3(+), CD4(+)CD8(-) single-positive (SP) cells was broken down into six discrete stages that were purified by four-color sorting: CD69(-)CD3(+)DP (stage 0), CD69(+)CD27(-)DP (stage 1), CD69(+)CD27(-)CD4(+)SP (stage 2), CD27(+)CD1(+)CD4(+)SP (stage 3), CD1(-)CD45RO(+) CD4(+)SP (stage 4), and CD1(-)CD45RO(-)CD4(+)SP cells (stage 5). Phenotypically, these stages seem to describe consecutive steps in differentiation from immature stage 0 to the terminally matured stage 5. Functionally, the capacity to proliferate on IL-2 after stimulation was absent in CD69(-) stage 0 cells, but was acquired gradually during stages 1 to 4. Clonal expandability and the capacity to respond to stimulation with the production of cytokines were acquired later and rather abruptly by CD1(-) stage 4 and 5 cells. Activation markers such as CD69 expression and in vivo IL-2 gene transcription came up simultaneously at the DP stage and peaked at stage 3 to 4. These data suggest that functional maturation of Th cells occurs over an extended period in differentiation, stages 1 to 4, and coincides with a gradual increase in activation markers. After completion of functional differentiation, at stage 5, in vivo IL-2 mRNA transcription and CD69 expression are down-regulated, and the cells become functionally resting naive T cells expressing CD45RA(+).
Keywords
MODEL, LYMPHOCYTES, SELECTION, EXPRESSION, HUMAN THYMOCYTES, RECEPTOR GAMMA-CHAIN, SCID-HU MOUSE, PRECURSORS, MATURATION, EVENTS

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Chicago
Vanhecke, Dominique, Bruno Verhasselt, Veronique Debacker, Georges Leclercq, Jean Plum, and Bart Vandekerckhove. 1995. “Differentiation to T Helper Cells in the Thymus : Gradual Acquisition of T Helper Cell Function by CD3+CD4+ Cells.” Journal of Immunology 155 (10): 4711–4718.
APA
Vanhecke, D., Verhasselt, B., Debacker, V., Leclercq, G., Plum, J., & Vandekerckhove, B. (1995). Differentiation to T helper cells in the thymus : gradual acquisition of T helper cell function by CD3+CD4+ cells. JOURNAL OF IMMUNOLOGY, 155(10), 4711–4718.
Vancouver
1.
Vanhecke D, Verhasselt B, Debacker V, Leclercq G, Plum J, Vandekerckhove B. Differentiation to T helper cells in the thymus : gradual acquisition of T helper cell function by CD3+CD4+ cells. JOURNAL OF IMMUNOLOGY. 1995;155(10):4711–8.
MLA
Vanhecke, Dominique, Bruno Verhasselt, Veronique Debacker, et al. “Differentiation to T Helper Cells in the Thymus : Gradual Acquisition of T Helper Cell Function by CD3+CD4+ Cells.” JOURNAL OF IMMUNOLOGY 155.10 (1995): 4711–4718. Print.
@article{262294,
  abstract     = {We investigated at which point during thymocyte differentiation functions were acquired that are characteristic for mature Th cells. Differentiation from CD3(+)CD69(-), CD4(+)CD8(+) double-positive (DP) cells to terminally differentiated CD3(+), CD4(+)CD8(-) single-positive (SP) cells was broken down into six discrete stages that were purified by four-color sorting: CD69(-)CD3(+)DP (stage 0), CD69(+)CD27(-)DP (stage 1), CD69(+)CD27(-)CD4(+)SP (stage 2), CD27(+)CD1(+)CD4(+)SP (stage 3), CD1(-)CD45RO(+) CD4(+)SP (stage 4), and CD1(-)CD45RO(-)CD4(+)SP cells (stage 5). Phenotypically, these stages seem to describe consecutive steps in differentiation from immature stage 0 to the terminally matured stage 5. Functionally, the capacity to proliferate on IL-2 after stimulation was absent in CD69(-) stage 0 cells, but was acquired gradually during stages 1 to 4. Clonal expandability and the capacity to respond to stimulation with the production of cytokines were acquired later and rather abruptly by CD1(-) stage 4 and 5 cells. Activation markers such as CD69 expression and in vivo IL-2 gene transcription came up simultaneously at the DP stage and peaked at stage 3 to 4. These data suggest that functional maturation of Th cells occurs over an extended period in differentiation, stages 1 to 4, and coincides with a gradual increase in activation markers. After completion of functional differentiation, at stage 5, in vivo IL-2 mRNA transcription and CD69 expression are down-regulated, and the cells become functionally resting naive T cells expressing CD45RA(+).},
  author       = {Vanhecke, Dominique and Verhasselt, Bruno and Debacker, Veronique and Leclercq, Georges and Plum, Jean and Vandekerckhove, Bart},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keyword      = {MODEL,LYMPHOCYTES,SELECTION,EXPRESSION,HUMAN THYMOCYTES,RECEPTOR GAMMA-CHAIN,SCID-HU MOUSE,PRECURSORS,MATURATION,EVENTS},
  language     = {eng},
  number       = {10},
  pages        = {4711--4718},
  title        = {Differentiation to T helper cells in the thymus : gradual acquisition of T helper cell function by CD3\unmatched{207a}CD4\unmatched{207a} cells},
  url          = {http://www.jimmunol.org/content/155/10/4711},
  volume       = {155},
  year         = {1995},
}