A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor.

Abstract

We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were present in spleen, mesenteric lymph nodes, peritoneal cavity, lamina propria and epithelial layer of the small and large intestine of 6- to 10-month-old, male and female tg scid mice. Only low numbers of CD3+ T cells were recovered from inguinal, popliteal, or axillary lymph nodes. We studied CD4+ T cells in these tg scid mice. CD4+ T cells were found in the peritoneal cavity, in the mesenteric lymph nodes and in the intraepithelial layer and lamina propria of the gut. All CD4+ T cells were CD44+ (i.e. showed evidence of antigen-driven differentiation) and expressed the tg V beta 8.2 TcR beta-chain (TcR beta T+). Only few CD4+ T cells expressed the tg V alpha 3+ TcR alpha-chain (TcR alpha T). cDNA was prepared from CD4+ T cells from spleen or mesenteric lymph nodes of individual male and female tg scid mice; sequence analyses of polymerase chain reaction-amplified, endogenous TcR alpha-chain (TcR alpha E) transcripts indicated that > 90% of the TcR alpha E-chain transcripts were in-frame, that the TcR alpha E repertoire in CD4+ T cell populations was oligoclonal, and that the TcR alpha E repertoire was different in individual tg scid mice. Hence, an oligoclonal, leaky CD4+ T cell population is selected in tg scid mice that apparently responds to gut-derived antigens. No inflammatory bowel disease (IBD) was evident in the small or large intestine of 6- to 10-month old tg scid mice. After adoptive transfer of purified CD4+ T cells (10(5) cells per mouse) from tg scid mice into non-tg H-2b scid mice, CD4+ TcR alpha T-beta T+ cells were found in gut tissues of the immunodeficient host. Transplanted scid mice developed clinical and histological signs of IBD. An oligoclonal, gut-homing, memory/effector CD4+ CD44+ TcR beta T+ TcR alpha T-T cell subset from leaky tg scid mice thus has a pathogenic potential when released from the control of TcR beta T+ TcR alpha T+ T cells.