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Rapid cytotoxic T lymphocyte activation occurs in the draining lymph nodes after cutaneous herpes simplex virus infection as a result of early antigen presentation and not the presence of virus.

Mueller SN, Jones CM, Smith CM, Heath WR, Carbone FR - J. Exp. Med. (2002)

Bottom Line: Furthermore, we show that T cell proliferation begins no sooner than 24 h after activation and is marked by the concurrent appearance of CTL activity in the PLNs.These events are not dependent on the presence of virus in the draining lymph nodes, and suggest a requirement for recruitment of professional antigen-presenting cells to the site of T cell activation.Consequently, we have defined the initiation of the CD8(+) T cell-mediated response to cutaneous HSV-1 infection, demonstrating that the immune response to localized viral infection depends only on the appearance of cells presenting virus-derived antigen and commences with remarkable swiftness.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, 3010, Australia.

ABSTRACT
Localized cutaneous herpes simplex virus type 1 (HSV-1) infection leads to arming and initial expansion of cytotoxic T lymphocytes (CTLs) in the draining popliteal lymph nodes (PLNs) followed by migration and further proliferation in the spleen. To accurately characterize the sequence of events involved in the activation and generation of anti-HSV CTLs, we used T cell receptor (TCR) transgenic mice specific for the immunodominant epitope from HSV glycoprotein B (gB(498-505)). We describe the detection of the initiation of antigen presentation in the draining lymph nodes by 4-6 h after infection with HSV-1. Analysis of CD69 up-regulation revealed activation of gB-specific CD8(+) T cells by 6-8 h after infection. Furthermore, we show that T cell proliferation begins no sooner than 24 h after activation and is marked by the concurrent appearance of CTL activity in the PLNs. These events are not dependent on the presence of virus in the draining lymph nodes, and suggest a requirement for recruitment of professional antigen-presenting cells to the site of T cell activation. Consequently, we have defined the initiation of the CD8(+) T cell-mediated response to cutaneous HSV-1 infection, demonstrating that the immune response to localized viral infection depends only on the appearance of cells presenting virus-derived antigen and commences with remarkable swiftness.

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Concurrent in vivo proliferation and CTL activity by gB-specific CD8+ T cells in the PLNs after cutaneous infection with HSV-1. (A) CFSE-labeled lymph node cells from gBT-I.1 mice were transferred into C57BL/6 mice before infection with HSV-1. PLN cells were isolated at various times after infection (24–72 h) and dilution of the CFSE fluorescence analyzed by gating on live CD8+ T cells. (B) Cellularity within the draining lymph nodes over a 48-h period was determined using cell suspensions obtained from the PLNs of mice after foot-pad HSV-1 infection. (C) Mice that had (black bars) or had not (white bars) received 106 gBT-I.1 cells 24 h earlier were infected with HSV-1 in the footpad and left for various times as shown before intravenous transfer of CFSE-labeled syngeneic target cells. gB-peptide–pulsed splenocytes were labeled with a high concentration of CFSE (CFSEhi) while unpulsed control targets were labeled with a low concentration of CFSE (CFSElo). 4 h after target cell transfer, mice were killed and PLN cells analyzed for relative elimination of the CFSEhi versus CFSElo populations. Percent specific lysis was calculated as described in reference 5. Error bars represent SD.
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fig1: Concurrent in vivo proliferation and CTL activity by gB-specific CD8+ T cells in the PLNs after cutaneous infection with HSV-1. (A) CFSE-labeled lymph node cells from gBT-I.1 mice were transferred into C57BL/6 mice before infection with HSV-1. PLN cells were isolated at various times after infection (24–72 h) and dilution of the CFSE fluorescence analyzed by gating on live CD8+ T cells. (B) Cellularity within the draining lymph nodes over a 48-h period was determined using cell suspensions obtained from the PLNs of mice after foot-pad HSV-1 infection. (C) Mice that had (black bars) or had not (white bars) received 106 gBT-I.1 cells 24 h earlier were infected with HSV-1 in the footpad and left for various times as shown before intravenous transfer of CFSE-labeled syngeneic target cells. gB-peptide–pulsed splenocytes were labeled with a high concentration of CFSE (CFSEhi) while unpulsed control targets were labeled with a low concentration of CFSE (CFSElo). 4 h after target cell transfer, mice were killed and PLN cells analyzed for relative elimination of the CFSEhi versus CFSElo populations. Percent specific lysis was calculated as described in reference 5. Error bars represent SD.

Mentions: To examine the early events that give rise to the large CTL pool detectable at the peak of the response to HSV-1 infection, gBT-I.1 CD8+ T cells were labeled with CFSE (14) and transferred into normal mice before footpad infection with HSV-1. The first appearance of a dividing cohort of CD8+ T cells appeared in the PLNs at ∼30 h after infection (Fig. 1 A). Progressive analysis indicated that these cells then proceeded to double consistently every 5–6 h thereafter, having undergone four divisions after 48 h and >7 divisions by 72 h. Initially, very few cells were present in the dividing pool, as indicated by the relatively small peak of divided cells at 30 h. However, as the response proceeded the number of cells that were recruited into the dividing pool continued to increase, thereby reducing the size of the undivided population.


Rapid cytotoxic T lymphocyte activation occurs in the draining lymph nodes after cutaneous herpes simplex virus infection as a result of early antigen presentation and not the presence of virus.

Mueller SN, Jones CM, Smith CM, Heath WR, Carbone FR - J. Exp. Med. (2002)

Concurrent in vivo proliferation and CTL activity by gB-specific CD8+ T cells in the PLNs after cutaneous infection with HSV-1. (A) CFSE-labeled lymph node cells from gBT-I.1 mice were transferred into C57BL/6 mice before infection with HSV-1. PLN cells were isolated at various times after infection (24–72 h) and dilution of the CFSE fluorescence analyzed by gating on live CD8+ T cells. (B) Cellularity within the draining lymph nodes over a 48-h period was determined using cell suspensions obtained from the PLNs of mice after foot-pad HSV-1 infection. (C) Mice that had (black bars) or had not (white bars) received 106 gBT-I.1 cells 24 h earlier were infected with HSV-1 in the footpad and left for various times as shown before intravenous transfer of CFSE-labeled syngeneic target cells. gB-peptide–pulsed splenocytes were labeled with a high concentration of CFSE (CFSEhi) while unpulsed control targets were labeled with a low concentration of CFSE (CFSElo). 4 h after target cell transfer, mice were killed and PLN cells analyzed for relative elimination of the CFSEhi versus CFSElo populations. Percent specific lysis was calculated as described in reference 5. Error bars represent SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193766&req=5

fig1: Concurrent in vivo proliferation and CTL activity by gB-specific CD8+ T cells in the PLNs after cutaneous infection with HSV-1. (A) CFSE-labeled lymph node cells from gBT-I.1 mice were transferred into C57BL/6 mice before infection with HSV-1. PLN cells were isolated at various times after infection (24–72 h) and dilution of the CFSE fluorescence analyzed by gating on live CD8+ T cells. (B) Cellularity within the draining lymph nodes over a 48-h period was determined using cell suspensions obtained from the PLNs of mice after foot-pad HSV-1 infection. (C) Mice that had (black bars) or had not (white bars) received 106 gBT-I.1 cells 24 h earlier were infected with HSV-1 in the footpad and left for various times as shown before intravenous transfer of CFSE-labeled syngeneic target cells. gB-peptide–pulsed splenocytes were labeled with a high concentration of CFSE (CFSEhi) while unpulsed control targets were labeled with a low concentration of CFSE (CFSElo). 4 h after target cell transfer, mice were killed and PLN cells analyzed for relative elimination of the CFSEhi versus CFSElo populations. Percent specific lysis was calculated as described in reference 5. Error bars represent SD.
Mentions: To examine the early events that give rise to the large CTL pool detectable at the peak of the response to HSV-1 infection, gBT-I.1 CD8+ T cells were labeled with CFSE (14) and transferred into normal mice before footpad infection with HSV-1. The first appearance of a dividing cohort of CD8+ T cells appeared in the PLNs at ∼30 h after infection (Fig. 1 A). Progressive analysis indicated that these cells then proceeded to double consistently every 5–6 h thereafter, having undergone four divisions after 48 h and >7 divisions by 72 h. Initially, very few cells were present in the dividing pool, as indicated by the relatively small peak of divided cells at 30 h. However, as the response proceeded the number of cells that were recruited into the dividing pool continued to increase, thereby reducing the size of the undivided population.

Bottom Line: Furthermore, we show that T cell proliferation begins no sooner than 24 h after activation and is marked by the concurrent appearance of CTL activity in the PLNs.These events are not dependent on the presence of virus in the draining lymph nodes, and suggest a requirement for recruitment of professional antigen-presenting cells to the site of T cell activation.Consequently, we have defined the initiation of the CD8(+) T cell-mediated response to cutaneous HSV-1 infection, demonstrating that the immune response to localized viral infection depends only on the appearance of cells presenting virus-derived antigen and commences with remarkable swiftness.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, 3010, Australia.

ABSTRACT
Localized cutaneous herpes simplex virus type 1 (HSV-1) infection leads to arming and initial expansion of cytotoxic T lymphocytes (CTLs) in the draining popliteal lymph nodes (PLNs) followed by migration and further proliferation in the spleen. To accurately characterize the sequence of events involved in the activation and generation of anti-HSV CTLs, we used T cell receptor (TCR) transgenic mice specific for the immunodominant epitope from HSV glycoprotein B (gB(498-505)). We describe the detection of the initiation of antigen presentation in the draining lymph nodes by 4-6 h after infection with HSV-1. Analysis of CD69 up-regulation revealed activation of gB-specific CD8(+) T cells by 6-8 h after infection. Furthermore, we show that T cell proliferation begins no sooner than 24 h after activation and is marked by the concurrent appearance of CTL activity in the PLNs. These events are not dependent on the presence of virus in the draining lymph nodes, and suggest a requirement for recruitment of professional antigen-presenting cells to the site of T cell activation. Consequently, we have defined the initiation of the CD8(+) T cell-mediated response to cutaneous HSV-1 infection, demonstrating that the immune response to localized viral infection depends only on the appearance of cells presenting virus-derived antigen and commences with remarkable swiftness.

Show MeSH
Related in: MedlinePlus