Lamina propria lymphocytes are derived from circulating cells that lack the Leu-8 lymph node homing receptor.
The Leu-8 membrane glycoprotein is the primate homologue of the murine MEL-14 peripheral lymph node homing receptor and is expressed on a majority of circulating lymphocytes but on few lymphocytes in the intestinal lamina propria. To examine the mechanisms regulating expression of the Leu-8-molecule on lymphocytes in different tissue sites, studies of Leu-8 membrane antigen expression, Leu-8 messenger RNA, and the Leu-8 gene were performed using normal human and nonhuman primate lymphocytes. Activation of resting peripheral blood lymphocytes caused a rapid decrease in membrane Leu-8 expression, a more gradual decrease in Leu-8 messenger RNA, and an increase in expression of interleukin 2 and interleukin 2 receptor messenger RNA. However, the down regulation of Leu-8 expression during activation was reversible because both membrane Leu-8 antigen and Leu-8 messenger RNA were reexpressed after 5 days of culture. Leu-8 messenger RNA was present in lymphocytes isolated from peripheral blood, spleen, and, particularly, mesenteric lymph node, but intestinal lamina propria lymphocytes contained very low levels of Leu-8 messenger RNA. The absence of Leu-8 messenger RNA in intestinal lymphocytes and circulating Leu-8 negative lymphocytes was not caused by recent activation in vivo because these cells did not have detectable interleukin 2 messenger RNA, and intestinal lymphocytes did not express Leu-8 after culture in vitro. Phorbol myristate acetate was found to be a strong inducer of Leu-8 messenger RNA in Leu-8-positive lymphocytes; however, phorbol myristate acetate did not induce membrane Leu-8 expression or Leu-8 messenger RNA in lamina propria lymphocytes. Leu-8-negative lymphocytes in peripheral blood or lamina propria did not have evidence of deletion or rearrangement of the Leu-8 gene. Leu-8-positive Jurkat cells and peripheral blood lymphocytes and Leu-8-negative peripheral blood and intestinal lymphocytes had partial methylation of an Msp I site in proximity to the Leu-8 gene, suggesting that in Leu-8-negative lymphocytes, the Leu-8 gene previously was transcriptionally active. In summary, these studies demonstrate that intestinal lamina propria lymphocytes have the same characteristics as circulating Leu-8-negative lymphocytes with respect to their state of activation and inability to express the Leu-8 antigen. The results suggest that the majority of lymphocytes that migrate to the intestinal lamina propria are derived from the subpopulation of circulating Leu-8-negative lymphocytes.
Berg
M
M
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
Murakawa
Y
Y
Camerini
D
D
James
S P
SP
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D000945:Antigens, Differentiation, T-Lymphocyte; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D013755:Tetradecanoylphorbol Acetate