CD4+ T cells with specific reactivity against astrovirus isolated from normal human small intestine

The gut is the largest immunologic organ in the human body, but little is known about the antigen specificity of mucosal T cells. This study sought to determine whether T cells resident in the duodenal mucosa could recognize astrovirus, a common and clinically important gastroenteritis virus. Serum antibodies against astrovirus are prevalent, indicating frequent viral exposure and postinfectious induction of systemic immune responses. Mucosal immune responses may conceivably mediate protection on astroviral reinfections.

Small intestinal biopsy specimens with normal histology were obtained from 8 adults and challenged in an organ culture system with inactivated human astrovirus. T cells activated by the viral challenge were isolated either by immunomagnetic positive selection of mucosal resident cells or by collecting cells emigrating into the culture supernatant.

Astrovirus-specific, mucosal T-cell lines were isolated from all 8 subjects. Analysis of 29 CD4+ T-cell clones from 3 subjects showed predominant HLA-DR restriction of astrovirus responses. Most of the T-cell clones showed a Th1-like cytokine profile when restimulated with astrovirus.

Helper T cells residing in normal, duodenal mucosa of adult subjects recognize a common enteropathogenic virus. These mucosal CD4+ T cells are presumably important in mucosal defense against recurrent astroviral infections.