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

We studied the peripheral T cell compartment of H-2(b) severe combined immunodeficient (acid) 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-2(b) 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.