Age-associated changes in the proliferative response of rat intestinal intraepithelial leukocytes to bacterial antigens

Abstract

Background & Aims : Intraepithelial leukocytes (IELs) residing in the intestinal epithelium are thought to recognize bacterial antigens and play an important role in providing protection against the invasion of microorganisms through the intestinal wall. This report studies the effect of various bacterial antigens on the proliferation of cultured IELs. Methods : Bacterial antigens, mycobacterial heat shock protein (hsp) 60 or 70, staphylococcal enteroxin A (SEA), or purified protein derivative (PPD) from Mycobacterium tuberculosis were added to mixed cultures of IELs and irradiated syngeneic or allogeneic spleen cells, and the proliferative response was evaluated. Monoclonal antibodies to CD4, CD8, and major histocompatibility complex class I or class II molecules were added to assess the role of these proteins in the proliferative response. Results : The proliferation of IELs isolated from mature rats in mixed culture was significantly enhanced by the addition of PPD, hsp 60, hsp 70, or SEA. The proliferation of mixed cultures of IELs isolated from young rats was enhanced only by the addition of SEA. In mixed cultures of mature rat IELs and syngeneic spleen cells containing PPD, proliferating populations were of the CD4 −CD8 + and CD4 +CD8 + phenotypes. Addition of anti-CD4 monoclonal antibody suppressed the proliferative response to PPD to control levels. Conclusions : IELs isolated from mature rats contain mycobacterial antigen-specific T cells, and these cells may be selected by long-term exposure to common intestinal bacterial antigens such as hsp. These cells may contain populations that recognize bacterial antigens in a CD4-dependent manner.