Details

Autor(en) / Beteiligte

• Schreurs, R R C E
• Sagebiel, A F
• Steinert, F L
• Highton, A J
• Klarenbeek, P L
• Drewniak, A
• Bakx, R
• The, S M L
• Ribeiro, C M S
• Perez, D
• Reinshagen, K
• Geijtenbeek, T B H
• van Goudoever, J B
• Bunders, M J

Titel

Intestinal CD8 + T cell responses are abundantly induced early in human development but show impaired cytotoxic effector capacities

Ist Teil von

• Mucosal immunology, 2021-05, Vol.14 (3), p.605-614

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8 T cells are critical to achieve viral control. However, studies investigating the development of CD8 T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8 T cell compartment in human fetal, infant and adult intestinal tissues. CD8 T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7 CD45RA CD127 KLRG1 CD8 T cells compared to tissue-resident memory CD69 CD103 CD8 T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8 T cells was, however, markedly reduced compared to adult intestinal CD8 T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8 T cells. Taken together, we demonstrate that intestinal CD8 T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8 T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.