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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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Triple color immunofluorescence analysis of cord blood  lymphocytes and PBMCs from an adult donor. Cells were simultaneously  stained with either CD4-PerCP or PerCP-labeled CD8 in combination  with PE-conjugated CD45RA and FITC-conjugated CD27 mAbs. Cells  were gated on forward scatter/side scatter and PerCP-fluorescence. Four  distinct populations can be defined within CD8+ cells from adult blood:  (1) CD45RA+CD27+ cells, (2) CD45RA−CD27+ cells, (3) CD45RA+  CD27− cells, and (4) CD45RA−CD27− cells. Note that there is also a  transitional population with dull CD45RA expression. As in the CD4+  subset (23), these cells have an intermediate phenotype for the studied surface  markers (data not shown). Functionally, this subset was not analyzed.
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Figure 1: Triple color immunofluorescence analysis of cord blood lymphocytes and PBMCs from an adult donor. Cells were simultaneously stained with either CD4-PerCP or PerCP-labeled CD8 in combination with PE-conjugated CD45RA and FITC-conjugated CD27 mAbs. Cells were gated on forward scatter/side scatter and PerCP-fluorescence. Four distinct populations can be defined within CD8+ cells from adult blood: (1) CD45RA+CD27+ cells, (2) CD45RA−CD27+ cells, (3) CD45RA+ CD27− cells, and (4) CD45RA−CD27− cells. Note that there is also a transitional population with dull CD45RA expression. As in the CD4+ subset (23), these cells have an intermediate phenotype for the studied surface markers (data not shown). Functionally, this subset was not analyzed.

Mentions: As has been previously noted (21), in contrast to CD4+CD27− T lymphocytes, which are exclusively CD45RA−, within the circulating CD8+ compartment CD27− T cells can be found within both CD45RA− and CD45RA+ fractions (Fig. 1). These CD8+CD45RA+CD27− cells are, like CD8+ CD45RA−CD45R0+ cells, absent from cord blood (Fig. 1). Therefore, we hypothesize that in response to antigen two separate primed CD8+ populations may develop in humans: (a) a population of CD45RA− T cells, and (b) a population of CD45RA+CD27− T cells. This study was performed to analyze whether these phenotypes discriminate between functionally distinct CD8+ subsets.


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)

Triple color immunofluorescence analysis of cord blood  lymphocytes and PBMCs from an adult donor. Cells were simultaneously  stained with either CD4-PerCP or PerCP-labeled CD8 in combination  with PE-conjugated CD45RA and FITC-conjugated CD27 mAbs. Cells  were gated on forward scatter/side scatter and PerCP-fluorescence. Four  distinct populations can be defined within CD8+ cells from adult blood:  (1) CD45RA+CD27+ cells, (2) CD45RA−CD27+ cells, (3) CD45RA+  CD27− cells, and (4) CD45RA−CD27− cells. Note that there is also a  transitional population with dull CD45RA expression. As in the CD4+  subset (23), these cells have an intermediate phenotype for the studied surface  markers (data not shown). Functionally, this subset was not analyzed.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Triple color immunofluorescence analysis of cord blood lymphocytes and PBMCs from an adult donor. Cells were simultaneously stained with either CD4-PerCP or PerCP-labeled CD8 in combination with PE-conjugated CD45RA and FITC-conjugated CD27 mAbs. Cells were gated on forward scatter/side scatter and PerCP-fluorescence. Four distinct populations can be defined within CD8+ cells from adult blood: (1) CD45RA+CD27+ cells, (2) CD45RA−CD27+ cells, (3) CD45RA+ CD27− cells, and (4) CD45RA−CD27− cells. Note that there is also a transitional population with dull CD45RA expression. As in the CD4+ subset (23), these cells have an intermediate phenotype for the studied surface markers (data not shown). Functionally, this subset was not analyzed.
Mentions: As has been previously noted (21), in contrast to CD4+CD27− T lymphocytes, which are exclusively CD45RA−, within the circulating CD8+ compartment CD27− T cells can be found within both CD45RA− and CD45RA+ fractions (Fig. 1). These CD8+CD45RA+CD27− cells are, like CD8+ CD45RA−CD45R0+ cells, absent from cord blood (Fig. 1). Therefore, we hypothesize that in response to antigen two separate primed CD8+ populations may develop in humans: (a) a population of CD45RA− T cells, and (b) a population of CD45RA+CD27− T cells. This study was performed to analyze whether these phenotypes discriminate between functionally distinct CD8+ subsets.

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