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Gastroenterology and Hepatology - Immunology - Infectious Diseases - Microbiology - Urology

Intraepithelial ?d T Cells Remain Increased in the Duodenum of AIDS Patients Despite Antiretroviral Treatment
Published: Wednesday, January 04, 2012
Author: Dag E. Nilssen et al.

by Dag E. Nilssen, Per Brandtzaeg

Intraepithelial lymphocytes (IELs) bearing the ?d T-cell receptor are a unique intestinal subset whose function remains elusive. Here, we examine how they behave in AIDS and during various regimens of antiretroviral treatment in order to obtain mechanistic insight into their adaptive or innate functional in vivo properties. IELs were studied by multimarker two-colour immunofluorescence in situ staining. Consecutive duodenal biopsies were obtained from advanced infection-prone HIV+ patients (n?=?30). The systemic adaptive immune status was monitored by determining T-cell subsets and immunoglobulins in peripheral blood. The ?d IEL ratio (median 14.5%, range 1.5–56.3%) was significantly increased (p<0.02) compared with that in clinically healthy HIV- control subjects (n?=?11, median 2.8%; range 0.3–38%), although the number of ?d IELs per mucosal length unit (U) only tended to be increased (4.0/U in HIV+ versus 3.2/U in HIV-subjects). Notably, the total number of CD3+ IELs was significantly reduced in AIDS (p<0.0001, 39.6/U in HIV+ versus 86.4/U in HIV- subjects). Almost 100% of the ?d IELs were CD8- and they often expressed the Vd1/Jd1-encoded epitope (median 65.2%). HIV+ patients on highly active antiretroviral therapy only tended to have a lower ratio of ?d IELs (median 12.8%) than those receiving no treatment (median 14.3%) or 1 nucleoside analogue (NA) (median 23.5%) or 2 NAs (median 13.0%). This minimal variation among therapy groups, contrasting the treatment response of systemic and local adaptive immunity, harmonizes with the novel idea derived from animal experiments that ?d T cells are largely innate cells in first-line microbial defence.