LIVER GAMMA-DELTA T-CELLS - TCR JUNCTIONS REVEAL DIFFERENCES IN HEAT-SHOCK PROTEIN-60-REACTIVE CELLS IN LIVER AND SPLEEN

The liver of mice contains elevated percentages of gammadelta T cells when compared with peripheral lymphoid organs. We have now analyzed th ese cells clonally, by generating a random collection of liver gammdel ta T cell hybridomas and sequencing the productively rearranged TCR-ga mma and -delta genes in each hybridoma clone. Examining C57BL/10 mice of various ages, we have found that over half of their normal gammadel ta T cells are one of two types, Vdelta4+ or Vdelta6.3+. gammadelta T cell hybridomas generated from mouse liver contain clones that are ''s pontaneously'' reactive, and respond to purified protein derivative fr om mycobacteria and to a 17-amino acid peptide from mycobacterial heat shock protein-60 (HSP-60). Like similar cells found in newborn thymus or adult spleen, all of the cells showing this HSP-60 reactivity patt ern were found to express Vgamma1-Jgamma4-Cgamma4, most in conjunction with Vdelta6-Jdelta1-Cdelta, particularly with Vdelta6.3. However, th e gamma and delta junctional sequences of the Vgamma1/Vdelta6+ cells i solated from adult liver differed from those found in adult spleen; be ing less diverse, their receptors instead resemble those of similar ce lls from newborn thymus. These data suggest that HSP-60-reactive gamma delta cells in adult murine liver and spleen are independent of each o ther and may be resident in their respective sites.