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CD2 sets quantitative thresholds in T cell activation.

Bachmann MF, Barner M, Kopf M - J. Exp. Med. (1999)

Bottom Line: This indicates that CD2 and LFA-1 facilitate T cell activation additively.In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming.Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, CH 4005 Basel, Switzerland. bachmann@bii.ch

ABSTRACT
It has been proposed that CD2, which is highly expressed on T cells, serves to enhance T cell-antigen presenting cell (APC) adhesion and costimulate T cell activation. Here we analyzed the role of CD2 using CD2-deficient mice crossed with transgenic mice expressing a T cell receptor specific for lymphocytic choriomeningitis virus (LCMV)-derived peptide p33. We found that absence of CD2 on T cells shifted the p33-specific dose-response curve in vitro by a factor of 3-10. In comparison, stimulation of T cells in the absence of lymphocyte function-associated antigen (LFA)-1-intercellular adhesion molecule (ICAM)-1 interaction shifted the dose-response curve by a factor of 10, whereas absence of both CD2-CD48 and LFA-1-ICAM-1 interactions shifted the response by a factor of approximately 100. This indicates that CD2 and LFA-1 facilitate T cell activation additively. T cell activation at low antigen density was blocked at its very first steps, as T cell APC conjugate formation, TCR triggering, and Ca(2+) fluxes were affected by the absence of CD2. In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming. Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.

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Normal in vivo expansion of LCMV-GP–specific, CD2-deficient, TCR-transgenic T cells upon infection with live virus. CD45.1+ TCR-transgenic control spleen cells were mixed 1:1 with CD45.1+ CD2-deficient spleen cells and adoptively transferred into C57BL/6 recipient mice. (A) Left panel: 1:1 distribution of CD2+ and CD2− TCR+ T cells was confirmed before transfer. Center and right panels: splenocytes from mice that received 106 cells of the mixture shown in the left panel 6 d earlier in the absence of an infection were stained for Vα2, CD8, and CD45.1 expression; <2% of CD8+Vα2+ T cells were derived from the adoptively transferred T cells. (B and C) Recipient mice were infected with LCMV (200 PFU; B) or recombinant vaccinia virus expressing LCMV-GP (2 × 106 PFU; C). CD45.1 expression was assessed for CD8+Vα2+ T cells, revealing expansion of CD2+ control T cells (upper right panels). CD2 expression was assessed similarly for CD8+Vα2+ T cells, revealing expansion of CD2-deficient T cells (lower right panels). Similar results were obtained 8 d after infection. One representative experiment of three is shown.
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Figure 7: Normal in vivo expansion of LCMV-GP–specific, CD2-deficient, TCR-transgenic T cells upon infection with live virus. CD45.1+ TCR-transgenic control spleen cells were mixed 1:1 with CD45.1+ CD2-deficient spleen cells and adoptively transferred into C57BL/6 recipient mice. (A) Left panel: 1:1 distribution of CD2+ and CD2− TCR+ T cells was confirmed before transfer. Center and right panels: splenocytes from mice that received 106 cells of the mixture shown in the left panel 6 d earlier in the absence of an infection were stained for Vα2, CD8, and CD45.1 expression; <2% of CD8+Vα2+ T cells were derived from the adoptively transferred T cells. (B and C) Recipient mice were infected with LCMV (200 PFU; B) or recombinant vaccinia virus expressing LCMV-GP (2 × 106 PFU; C). CD45.1 expression was assessed for CD8+Vα2+ T cells, revealing expansion of CD2+ control T cells (upper right panels). CD2 expression was assessed similarly for CD8+Vα2+ T cells, revealing expansion of CD2-deficient T cells (lower right panels). Similar results were obtained 8 d after infection. One representative experiment of three is shown.

Mentions: To assess the role of CD2 in viral infections, an adoptive transfer system was employed 239. Spleen cells (106) from TCR-transgenic CD2-deficient and control mice were mixed at a 1:1 ratio and adoptively transferred into nonirradiated C57BL/6 mice and immunized with LCMV (200 PFU) or a recombinant vaccinia virus expressing LCMV-GP (Vacc-GP; 2 × 106 PFU). To enable selective identification of the control versus CD2-deficient TCR-transgenic T cells, TCR-transgenic control mice on a CD45.1 background were used. Expansion of transferred TCR-transgenic control and CD2-deficient T cells was subsequently assessed 6 (Fig. 7) or 8 d (not shown) later. No significant difference between CD2-deficient and control T cells was observed. These results are in agreement with an earlier report, in which CD2-deficient mice were found to mount normal LCMV-specific CD8+ T cell responses 27. Surprisingly, even the absence of both functional CD2 and LFA-1 together also failed to interfere with the response, as CD2-deficient T cells transferred into ICAM-1–deficient mice expanded normally upon infection with LCMV or Vacc-GP (not shown).


CD2 sets quantitative thresholds in T cell activation.

Bachmann MF, Barner M, Kopf M - J. Exp. Med. (1999)

Normal in vivo expansion of LCMV-GP–specific, CD2-deficient, TCR-transgenic T cells upon infection with live virus. CD45.1+ TCR-transgenic control spleen cells were mixed 1:1 with CD45.1+ CD2-deficient spleen cells and adoptively transferred into C57BL/6 recipient mice. (A) Left panel: 1:1 distribution of CD2+ and CD2− TCR+ T cells was confirmed before transfer. Center and right panels: splenocytes from mice that received 106 cells of the mixture shown in the left panel 6 d earlier in the absence of an infection were stained for Vα2, CD8, and CD45.1 expression; <2% of CD8+Vα2+ T cells were derived from the adoptively transferred T cells. (B and C) Recipient mice were infected with LCMV (200 PFU; B) or recombinant vaccinia virus expressing LCMV-GP (2 × 106 PFU; C). CD45.1 expression was assessed for CD8+Vα2+ T cells, revealing expansion of CD2+ control T cells (upper right panels). CD2 expression was assessed similarly for CD8+Vα2+ T cells, revealing expansion of CD2-deficient T cells (lower right panels). Similar results were obtained 8 d after infection. One representative experiment of three is shown.
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Related In: Results  -  Collection

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Figure 7: Normal in vivo expansion of LCMV-GP–specific, CD2-deficient, TCR-transgenic T cells upon infection with live virus. CD45.1+ TCR-transgenic control spleen cells were mixed 1:1 with CD45.1+ CD2-deficient spleen cells and adoptively transferred into C57BL/6 recipient mice. (A) Left panel: 1:1 distribution of CD2+ and CD2− TCR+ T cells was confirmed before transfer. Center and right panels: splenocytes from mice that received 106 cells of the mixture shown in the left panel 6 d earlier in the absence of an infection were stained for Vα2, CD8, and CD45.1 expression; <2% of CD8+Vα2+ T cells were derived from the adoptively transferred T cells. (B and C) Recipient mice were infected with LCMV (200 PFU; B) or recombinant vaccinia virus expressing LCMV-GP (2 × 106 PFU; C). CD45.1 expression was assessed for CD8+Vα2+ T cells, revealing expansion of CD2+ control T cells (upper right panels). CD2 expression was assessed similarly for CD8+Vα2+ T cells, revealing expansion of CD2-deficient T cells (lower right panels). Similar results were obtained 8 d after infection. One representative experiment of three is shown.
Mentions: To assess the role of CD2 in viral infections, an adoptive transfer system was employed 239. Spleen cells (106) from TCR-transgenic CD2-deficient and control mice were mixed at a 1:1 ratio and adoptively transferred into nonirradiated C57BL/6 mice and immunized with LCMV (200 PFU) or a recombinant vaccinia virus expressing LCMV-GP (Vacc-GP; 2 × 106 PFU). To enable selective identification of the control versus CD2-deficient TCR-transgenic T cells, TCR-transgenic control mice on a CD45.1 background were used. Expansion of transferred TCR-transgenic control and CD2-deficient T cells was subsequently assessed 6 (Fig. 7) or 8 d (not shown) later. No significant difference between CD2-deficient and control T cells was observed. These results are in agreement with an earlier report, in which CD2-deficient mice were found to mount normal LCMV-specific CD8+ T cell responses 27. Surprisingly, even the absence of both functional CD2 and LFA-1 together also failed to interfere with the response, as CD2-deficient T cells transferred into ICAM-1–deficient mice expanded normally upon infection with LCMV or Vacc-GP (not shown).

Bottom Line: This indicates that CD2 and LFA-1 facilitate T cell activation additively.In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming.Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, CH 4005 Basel, Switzerland. bachmann@bii.ch

ABSTRACT
It has been proposed that CD2, which is highly expressed on T cells, serves to enhance T cell-antigen presenting cell (APC) adhesion and costimulate T cell activation. Here we analyzed the role of CD2 using CD2-deficient mice crossed with transgenic mice expressing a T cell receptor specific for lymphocytic choriomeningitis virus (LCMV)-derived peptide p33. We found that absence of CD2 on T cells shifted the p33-specific dose-response curve in vitro by a factor of 3-10. In comparison, stimulation of T cells in the absence of lymphocyte function-associated antigen (LFA)-1-intercellular adhesion molecule (ICAM)-1 interaction shifted the dose-response curve by a factor of 10, whereas absence of both CD2-CD48 and LFA-1-ICAM-1 interactions shifted the response by a factor of approximately 100. This indicates that CD2 and LFA-1 facilitate T cell activation additively. T cell activation at low antigen density was blocked at its very first steps, as T cell APC conjugate formation, TCR triggering, and Ca(2+) fluxes were affected by the absence of CD2. In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming. Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.

Show MeSH
Related in: MedlinePlus