Peripheral Thy1+ lymphocytes rearranging TCR-gammadelta genes in LAT-deficient mice.
Linker for activation of T cells (LAT) is an adaptor molecule indispensable for development of alphabeta and gammadelta T lymphocytes. Surprisingly, using a new model of LAT-deficient mice we found that despite arrested thymic development, a discrete population of cells with active Lat promoter, expressing Thy1 molecules, accumulated in peripheral lymphoid organs of homozygous (Lat(Inv/Inv)) mutant mice. By measuring frequencies of TCR gene rearrangements in conjunction with a panel of cell surface Ag, we dissected two subsets of these Thy1(+) cells. Thy1(dull) cells expressed markers of NK lymphocytes and contained low frequency of TCR-gamma gene rearrangements without detectable TCR-delta rearrangements. Thy1(high) cells resembled immature CD44(+)CD25(+) thymocytes and contained high frequency of non-productive TCR-gamma and TCR-delta rearrangements, indicating that cells displaying molecular signatures of commitment toward gammadelta T-cell lineage can develop and populate lymphoid tissues of LAT-deficient mice. Phenotypically similar Thy1(high) cells were also found in lymph nodes of lymphocyte-deficient (Rag2(-/-)) mice but not in T lymphocyte proficient, heterozygous Lat(+/Inv) mice suggesting that Thy1(high) cells of LAT-deficient mice identified in this study accumulate in peripheral lymphoid organs as a result of congenital lymphopenia.
Miazek
Arkadiusz
A
Department of Tumor Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Macha
Kornelia
K
Łaszkiewicz
Agnieszka
A
Kissenpfennig
Adrien
A
Malissen
Bernard
B
Kisielow
Pawel
P
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens / Q000096:biosynthesis* / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018800:Thy-1 Antigens