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Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help.

Bennett SR, Carbone FR, Karamalis F, Miller JF, Heath WR - J. Exp. Med. (1997)

Bottom Line: The related effect of cross-tolerance can also effectively eliminate responses to selected self components.Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC.Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

View Article: PubMed Central - PubMed

Affiliation: Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia.

ABSTRACT
Class I-restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I-restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate responses to selected self components. In both cases, this presentation appears to require the active involvement of a bone marrow-derived antigen presenting cell (APC). Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells. Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

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OVA-specific cross-priming requires CD4+ T cell help in  vivo. Normal B6 mice (circles) or mice depleted of CD4+ T cells by twice  weekly intraperitoneal injections of GK1.5 ascites (squares) were immunized intravenously with 2.5 × 107 OVA-loaded spleen cells. 7 d later,  their spleens were removed and either left intact (a) or depleted of CD4+  T cells by treatment with RL172 antibody and complement (b). After 6 d  in vitro stimulation with OVA-loaded spleen cells, a CTL assay using  OVA257-264-pulsed EL4 (closed symbols) and EL4 (open symbols) targets was  performed. This experiment was performed four times with 2–3 mice/ group.
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Figure 3: OVA-specific cross-priming requires CD4+ T cell help in vivo. Normal B6 mice (circles) or mice depleted of CD4+ T cells by twice weekly intraperitoneal injections of GK1.5 ascites (squares) were immunized intravenously with 2.5 × 107 OVA-loaded spleen cells. 7 d later, their spleens were removed and either left intact (a) or depleted of CD4+ T cells by treatment with RL172 antibody and complement (b). After 6 d in vitro stimulation with OVA-loaded spleen cells, a CTL assay using OVA257-264-pulsed EL4 (closed symbols) and EL4 (open symbols) targets was performed. This experiment was performed four times with 2–3 mice/ group.

Mentions: To determine whether CD4+ T cell help was required for the generation of OVA-specific CTL by cross-priming with OVA-loaded spleen cells, this response was examined in CD4+ T cell–depleted B6 mice (Fig. 3 a). The failure to generate OVA-specific CTL under these conditions indicated that CD4+ T cells were essential for CTL priming. This requirement was only apparent for in vivo priming, since depletion of CD4+ T cells during the in vitro culture period did not prevent the generation of CTL (Fig. 3 b).


Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help.

Bennett SR, Carbone FR, Karamalis F, Miller JF, Heath WR - J. Exp. Med. (1997)

OVA-specific cross-priming requires CD4+ T cell help in  vivo. Normal B6 mice (circles) or mice depleted of CD4+ T cells by twice  weekly intraperitoneal injections of GK1.5 ascites (squares) were immunized intravenously with 2.5 × 107 OVA-loaded spleen cells. 7 d later,  their spleens were removed and either left intact (a) or depleted of CD4+  T cells by treatment with RL172 antibody and complement (b). After 6 d  in vitro stimulation with OVA-loaded spleen cells, a CTL assay using  OVA257-264-pulsed EL4 (closed symbols) and EL4 (open symbols) targets was  performed. This experiment was performed four times with 2–3 mice/ group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198964&req=5

Figure 3: OVA-specific cross-priming requires CD4+ T cell help in vivo. Normal B6 mice (circles) or mice depleted of CD4+ T cells by twice weekly intraperitoneal injections of GK1.5 ascites (squares) were immunized intravenously with 2.5 × 107 OVA-loaded spleen cells. 7 d later, their spleens were removed and either left intact (a) or depleted of CD4+ T cells by treatment with RL172 antibody and complement (b). After 6 d in vitro stimulation with OVA-loaded spleen cells, a CTL assay using OVA257-264-pulsed EL4 (closed symbols) and EL4 (open symbols) targets was performed. This experiment was performed four times with 2–3 mice/ group.
Mentions: To determine whether CD4+ T cell help was required for the generation of OVA-specific CTL by cross-priming with OVA-loaded spleen cells, this response was examined in CD4+ T cell–depleted B6 mice (Fig. 3 a). The failure to generate OVA-specific CTL under these conditions indicated that CD4+ T cells were essential for CTL priming. This requirement was only apparent for in vivo priming, since depletion of CD4+ T cells during the in vitro culture period did not prevent the generation of CTL (Fig. 3 b).

Bottom Line: The related effect of cross-tolerance can also effectively eliminate responses to selected self components.Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC.Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

View Article: PubMed Central - PubMed

Affiliation: Thymus Biology Unit, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia.

ABSTRACT
Class I-restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I-restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate responses to selected self components. In both cases, this presentation appears to require the active involvement of a bone marrow-derived antigen presenting cell (APC). Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells. Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.

Show MeSH
Related in: MedlinePlus