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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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Proliferative capacity of CD8+ T cell subsets. Purified CD8+  T cells were sorted into the indicated subsets and stimulated with a combination of three CD2 mAbs in the presence of different cytokines. Proliferation was measured on day 4 by adding [3H]thymidine during the last  4 h of the culture. Results from one out of three experiments are shown.
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Figure 4: Proliferative capacity of CD8+ T cell subsets. Purified CD8+ T cells were sorted into the indicated subsets and stimulated with a combination of three CD2 mAbs in the presence of different cytokines. Proliferation was measured on day 4 by adding [3H]thymidine during the last 4 h of the culture. Results from one out of three experiments are shown.

Mentions: To test if the distinction in cytokine production profiles between the two primed CD8+ T cell subpopulations was reflected in their proliferation capacities, three fractions were sorted from purified CD8+ T cells, i.e., CD45RA+CD27+, CD45RA+CD27−, and CD45RA−CD27+ cells, and stimulated with a combination of CD2 mAbs supplemented with various cytokines (Fig. 4). The CD45RA−CD27− population could not be analyzed because of the low number of these cells in most donors (see above). Culture of the sorted cells with the indicated cytokines alone did not result in proliferation (data not shown). In accordance with a previous report (18) on stringent activation requirements of unprimed CD8+ T cells, CD45RA+CD27+ cells were not able to proliferate in response to CD2 mAbs alone, but addition of IL-2, -15, -4, and, to a lesser extent, -12 resulted in a vigorous proliferative response, whereas IL-6 and -10 and IFN-γ had no effect on proliferation. In contrast, CD2 mAbs alone were sufficient to induce proliferation of CD45RA−CD27+ cells. IL-2, -15, and -12 further increased proliferation, but IL-4, -6, and -10, and IFN-γ only marginally influenced the CD2-induced response. Proliferation of CD45RA+CD27− cells was only observed in the presence of either IL-2 or -15. However, the magnitude of the response was lower than that of the other two populations.


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)

Proliferative capacity of CD8+ T cell subsets. Purified CD8+  T cells were sorted into the indicated subsets and stimulated with a combination of three CD2 mAbs in the presence of different cytokines. Proliferation was measured on day 4 by adding [3H]thymidine during the last  4 h of the culture. Results from one out of three experiments are shown.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Proliferative capacity of CD8+ T cell subsets. Purified CD8+ T cells were sorted into the indicated subsets and stimulated with a combination of three CD2 mAbs in the presence of different cytokines. Proliferation was measured on day 4 by adding [3H]thymidine during the last 4 h of the culture. Results from one out of three experiments are shown.
Mentions: To test if the distinction in cytokine production profiles between the two primed CD8+ T cell subpopulations was reflected in their proliferation capacities, three fractions were sorted from purified CD8+ T cells, i.e., CD45RA+CD27+, CD45RA+CD27−, and CD45RA−CD27+ cells, and stimulated with a combination of CD2 mAbs supplemented with various cytokines (Fig. 4). The CD45RA−CD27− population could not be analyzed because of the low number of these cells in most donors (see above). Culture of the sorted cells with the indicated cytokines alone did not result in proliferation (data not shown). In accordance with a previous report (18) on stringent activation requirements of unprimed CD8+ T cells, CD45RA+CD27+ cells were not able to proliferate in response to CD2 mAbs alone, but addition of IL-2, -15, -4, and, to a lesser extent, -12 resulted in a vigorous proliferative response, whereas IL-6 and -10 and IFN-γ had no effect on proliferation. In contrast, CD2 mAbs alone were sufficient to induce proliferation of CD45RA−CD27+ cells. IL-2, -15, and -12 further increased proliferation, but IL-4, -6, and -10, and IFN-γ only marginally influenced the CD2-induced response. Proliferation of CD45RA+CD27− cells was only observed in the presence of either IL-2 or -15. However, the magnitude of the response was lower than that of the other two populations.

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