Airway Eosinophils Accumulate in the Mediastinal Lymph Nodes but Lack Antigen-Presenting Potential for Naive T Cells

Abstract

Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed T cells in draining lymph nodes (DLN) of the lung and compared this capacity with professional dendritic cells (DC). During development of eosinophilic airway inflammation in OVA-sensitized and challenged mice, CCR3+ eosinophils accumulated in the DLN. To study their function, eosinophils were isolated from the bronchoalveolar lavage fluid of mice by sorting on CCR3+B220−CD3−CD11cdim low autofluorescent cells, avoiding contamination with other APCs, and were intratracheally injected into mice that previously received CFSE-labeled OVA TCR-transgenic T cells. Eosinophils did not induce divisions of T cells in the DLN, whereas DC induced on average 3.7 divisions in 45.7% of T cells. To circumvent the need for Ag processing or migration in vivo, eosinophils were pulsed with OVA peptide and were still not able to induce T cell priming in vitro, whereas DC induced vigorous proliferation. This lack of Ag-presenting ability was explained by the very weak expression of MHC class II on fresh eosinophils, despite expression of the costimulatory molecules CD80 and ICAM-1. This investigation does not support any role for airway eosinophils as APCs to naive T cells, despite their migration to the DLN at times of allergen exposure. DC are clearly superior in activating T cells in the DLN of the lung.

Effective antigen presentation to helper T cells by human eosinophils

“…(21) We show here that human eosinophils are also effective APC for a variety of antigens in vitro, able to evoke Th proliferative responses comparable in magnitude to those seen when paired PMBC samples are challenged with the same antigen. Thus, human eosinophil presentation to Th cells is limited neither to peptide antigens nor superantigens that do not require processing, as has been suggested, (11,16) but may instead contribute to responses against many different proteins. Whether such activity as APC in vitro is replicated in vivo remains to be established, but would be consistent with the increasingly accepted view that human eosinophils have immune regulatory, as well as effector, roles.…”

“…(15) Consistent with APC function, murine eosinophils home to lymphoid tissue and provide a second signal for T cell activation through the expression of key co-stimulatory molecules such as CD80 and CD86. (16,17) Although it has been demonstrated that human eosinophils can express CD86 when taken from hypereosinophilic patients, (18) or stimulated with IL-3, (19) it is unclear how commonly, or in what circumstances, they display such co-stimulatory molecules. There are also reports that human eosinophils can process and present antigen to activate specific T cells, (20) but, again, it remains to be established how widespread is such ability in different individuals and for different antigens.…”

“…Despite the evidence that eosinophils have the potential to act as APC to drive Th cell responses and thereby propagate inflammation, (21,22) other findings have suggested that this is limited to super-antigens and peptides, rather than proteins that require processing. (11,16) The effects of Th activation are critically dependent on the subset(s) that respond, and the associated cytokines they produce, but it is not known whether eosinophil antigen presentation preferentially supports responses by any particular Th type.…”

The rise of the phoenix: the expanding role of the eosinophil in health and disease

“…Studies in mice have shown that eosinophils are capable of transmigrating to lymphoid tissues and presenting antigens to lymphocytes (71,72). Although antigen presentation to naı¨ve T cells by eosinophils is still controversial, there is a consensus that eosinophils can present antigen to previously activated T cells, supporting the notion that eosinophils can further influence established immune responses (73).…”

Prenatal Stress Enhances Susceptibility of Murine Adult Offspring toward Airway Inflammation

“…Because the chemokine receptor CCR3 has been proposed to orchestrate eosinophil migration into the lung, we investigated the percentage of CCR3-expressing leukocytes in lung tissue after enzymatic digestion (31). In prenatally stressed mice, an increased percentage of chemokine receptor CCR3 ϩ cells among lungderived leukocytes could be detected (Fig.…”