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Phenotypic and functional separation of memory and effector human CD8+ T cells.

Hamann D, Baars PA, Rep MH, Hooibrink B, Kerkhof-Garde SR, Klein MR, van Lier RA - J. Exp. Med. (1997)

Bottom Line: These T cells do not secrete IL-2 or -4 but can produce IFN-gamma and TNF-alpha.Interestingly, CD8+CD45RA+CD27- cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation.Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.

ABSTRACT
Human CD8+ memory- and effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8+ T cell subset. First, CD45RA-CD45R0(+) cells are reminiscent of memory-type T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon gamma, tumor necrosis factor alpha, and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8+CD45RA+CD27- population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFN-gamma and TNF-alpha. In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8+CD45RA+CD27- cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.

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Related in: MedlinePlus

Helper and suppressor capacities of CD8+ T cell subsets. B  cells were cocultured with the indicated T cell subsets in CD3-coated wells  for 14 d. Ig content of the supernatant was measured with specific ELISAs. (A) Cells of the different T cell populations were cultured with B  cells alone to determine their helper capacities. (B) Cells of the distinct  CD8+ subsets were added to the coculture of autologous B and CD4+ T  cells to measure their suppressor activity. One out of two comparable experiments is shown. The distribution of cells in the different subsets was as  follows: CD45RA+CD27+, 50%; CD45RA+CD27−, 5%; and CD45RA−  CD27+, 35%.
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Figure 8: Helper and suppressor capacities of CD8+ T cell subsets. B cells were cocultured with the indicated T cell subsets in CD3-coated wells for 14 d. Ig content of the supernatant was measured with specific ELISAs. (A) Cells of the different T cell populations were cultured with B cells alone to determine their helper capacities. (B) Cells of the distinct CD8+ subsets were added to the coculture of autologous B and CD4+ T cells to measure their suppressor activity. One out of two comparable experiments is shown. The distribution of cells in the different subsets was as follows: CD45RA+CD27+, 50%; CD45RA+CD27−, 5%; and CD45RA− CD27+, 35%.

Mentions: Apart from their cytolytic capacities, CD8+ cells have been shown to exert suppressor activity as well as helper activity for Ig synthesis (43). Helper capacity of CD8+ T cell subsets was tested in a CD3 mAb–driven T cell–dependent B cell differentiation assay (44). When total CD4+ and CD8+ cells were compared, helper activity was preferentially found in the CD4+ fraction (Fig. 8 A). However, when CD8+ cells were further separated into the indicated subsets, it was found that the CD45RA−CD27+ cells were also able to support B cell differentiation, whereas both the CD45RA+CD27+ and the CD45RA+CD27− cells showed no helper activity.


Phenotypic and functional separation of memory and effector human CD8+ T cells.

Hamann D, Baars PA, Rep MH, Hooibrink B, Kerkhof-Garde SR, Klein MR, van Lier RA - J. Exp. Med. (1997)

Helper and suppressor capacities of CD8+ T cell subsets. B  cells were cocultured with the indicated T cell subsets in CD3-coated wells  for 14 d. Ig content of the supernatant was measured with specific ELISAs. (A) Cells of the different T cell populations were cultured with B  cells alone to determine their helper capacities. (B) Cells of the distinct  CD8+ subsets were added to the coculture of autologous B and CD4+ T  cells to measure their suppressor activity. One out of two comparable experiments is shown. The distribution of cells in the different subsets was as  follows: CD45RA+CD27+, 50%; CD45RA+CD27−, 5%; and CD45RA−  CD27+, 35%.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199103&req=5

Figure 8: Helper and suppressor capacities of CD8+ T cell subsets. B cells were cocultured with the indicated T cell subsets in CD3-coated wells for 14 d. Ig content of the supernatant was measured with specific ELISAs. (A) Cells of the different T cell populations were cultured with B cells alone to determine their helper capacities. (B) Cells of the distinct CD8+ subsets were added to the coculture of autologous B and CD4+ T cells to measure their suppressor activity. One out of two comparable experiments is shown. The distribution of cells in the different subsets was as follows: CD45RA+CD27+, 50%; CD45RA+CD27−, 5%; and CD45RA− CD27+, 35%.
Mentions: Apart from their cytolytic capacities, CD8+ cells have been shown to exert suppressor activity as well as helper activity for Ig synthesis (43). Helper capacity of CD8+ T cell subsets was tested in a CD3 mAb–driven T cell–dependent B cell differentiation assay (44). When total CD4+ and CD8+ cells were compared, helper activity was preferentially found in the CD4+ fraction (Fig. 8 A). However, when CD8+ cells were further separated into the indicated subsets, it was found that the CD45RA−CD27+ cells were also able to support B cell differentiation, whereas both the CD45RA+CD27+ and the CD45RA+CD27− cells showed no helper activity.

Bottom Line: These T cells do not secrete IL-2 or -4 but can produce IFN-gamma and TNF-alpha.Interestingly, CD8+CD45RA+CD27- cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation.Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.

ABSTRACT
Human CD8+ memory- and effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8+ T cell subset. First, CD45RA-CD45R0(+) cells are reminiscent of memory-type T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon gamma, tumor necrosis factor alpha, and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8+CD45RA+CD27- population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFN-gamma and TNF-alpha. In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8+CD45RA+CD27- cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.

Show MeSH
Related in: MedlinePlus