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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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(A) CD8+ T cell  subsets differ in Fas expression.  (B) Fas ligand (FasL) and HPRT  (hypoxanthine-guanine phosphoribosyltransferase) mRNA expression in sorted CD8+ T cell  subsets as assessed by RT-PCR.  Lane A, CD8 total; lane B,  CD8+ CD45RA+CD27+; lane C,  CD8+ CD45RA+CD27−; lane  D, CD8+ CD45RA−CD27+.
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Figure 2: (A) CD8+ T cell subsets differ in Fas expression. (B) Fas ligand (FasL) and HPRT (hypoxanthine-guanine phosphoribosyltransferase) mRNA expression in sorted CD8+ T cell subsets as assessed by RT-PCR. Lane A, CD8 total; lane B, CD8+ CD45RA+CD27+; lane C, CD8+ CD45RA+CD27−; lane D, CD8+ CD45RA−CD27+.

Mentions: Fas (CD95) was not expressed on CD8+CD45RA+ CD27+ lymphocytes but could be detected on the majority of CD45RA+CD27− T cells. It should be noted that the antigen density on the latter population was markedly lower than on CD8+CD45RA− T cells (Table 1 and Fig. 2 A). Interestingly, Fas ligand mRNA was not present in CD8+CD45RA+CD27+ T cells but was strongly expressed in CD8+CD45RA+CD27− lymphocytes (Fig. 2 B, lanes B and C). In contrast, only trace amounts of Fas ligand mRNA were detected in CD8+CD45RA−CD27+ cells (Fig. 2 B, lane D).


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)

(A) CD8+ T cell  subsets differ in Fas expression.  (B) Fas ligand (FasL) and HPRT  (hypoxanthine-guanine phosphoribosyltransferase) mRNA expression in sorted CD8+ T cell  subsets as assessed by RT-PCR.  Lane A, CD8 total; lane B,  CD8+ CD45RA+CD27+; lane C,  CD8+ CD45RA+CD27−; lane  D, CD8+ CD45RA−CD27+.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: (A) CD8+ T cell subsets differ in Fas expression. (B) Fas ligand (FasL) and HPRT (hypoxanthine-guanine phosphoribosyltransferase) mRNA expression in sorted CD8+ T cell subsets as assessed by RT-PCR. Lane A, CD8 total; lane B, CD8+ CD45RA+CD27+; lane C, CD8+ CD45RA+CD27−; lane D, CD8+ CD45RA−CD27+.
Mentions: Fas (CD95) was not expressed on CD8+CD45RA+ CD27+ lymphocytes but could be detected on the majority of CD45RA+CD27− T cells. It should be noted that the antigen density on the latter population was markedly lower than on CD8+CD45RA− T cells (Table 1 and Fig. 2 A). Interestingly, Fas ligand mRNA was not present in CD8+CD45RA+CD27+ T cells but was strongly expressed in CD8+CD45RA+CD27− lymphocytes (Fig. 2 B, lanes B and C). In contrast, only trace amounts of Fas ligand mRNA were detected in CD8+CD45RA−CD27+ cells (Fig. 2 B, lane D).

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