Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help

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.

Maintenance of memory CTL responses by T helper cells and CD40‐CD40 ligand: antibodies provide the key

“…1A, C). These results confirm that antiviral CTL responses can develop normally in the absence of CD4 + T cells and CD40 or its ligand [21,32] and stands in sharp contrast to CTL responses against tumor antigens and other weak CTL antigens, which require the presence of CD4 + T cells for efficient induction [6][7][8][9].…”

“…Activation of antigen-presenting cells (APC) such as dendritic cells (DC) is probably important for both antiviral and anti-tumor immunity [5]. In fact, for induction of CTL responses against tumors, the activation of APC by Th cells via CD40-CD40 ligand (CD40L) interaction appears to be an essential pathway [6][7][8][9]. In contrast, viruses have many means for CD40-independent APC activation including double-stranded RNA [10,11] and cytokines produced by infected cells, which can directly activate APC [12,13].…”

Type I interferons suppress CD4+ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

“…Our data indicate that CD4 1 T cells provide essential help during the first 2 days of infection for the generation of pathogenic CD8 1 T-cell responses. CD4 1 T-cell help to CD8 1 T-cell responses is a well-established phenomenon, often involving co-stimulatory molecules and cytokines, such as IL-2 [46][47][48][49]. The molecules involved in signalling between CD4 1 T cells and CD8 1 T cells during blood-stage Plasmodium infection remain to be defined.…”

Gene gun-mediated DNA vaccination induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs

“…The enhanced CD4 presentation by LAMP-1 can help the induction of CD8 + CTL responses by cross-priming. 39 Thus, CD4 + cellmediated help may be more important for cross-priming…”