| Popis: |
In addition to the major T lymphocyte population, expressing surface receptors (TCR) for antigen/MHC composed of a disulphide-linked heterodimer (alpha/beta chains), a minor subset has recently been identified which expresses a different form (gamma/delta) of CD3-associated molecules (Brenner 1986, 1987). Different molecular forms of TCR gamma/delta have been identified by the use of anti-TCR gamma/delta mAbs (Bottino 1988, Hochstenbach 1988, Moretta A. 1988). Thus, BB3 (Ciccone 1988a) and A13 (Ferrini 1989) mAbs (or analogous delta-TCS1) have been shown to recognize two non-overlapping lymphocyte subsets (Bottino 1988) of peripheral blood-derived TCR gamma-delta+ cells. BB3 mAb have been shown to specifically recognize Vdelta2 expressing cells, on the other hand A13 recognizes Vdeltal+ lymphocytes. More than 95% of TCR gamma/delta+ lymphocytes in the peripheral blood belong to the BB3+ or A13+ cells. In the peripheral blood molecules reactive with BB3 mAb correlate with the disulphide-linked (Cγ1 encoded) form of the receptor, whereas A13 reacts with two distinct non disulphide-linked (Cγ2 encoded) forms of TCR gamma/delta. Although in the first functional studies the MHC-unrestricted cytolytic activity of these cells was emphasized (Borst 1987), recently evidence has been provided both in man and in mouse that TCR gamma/delta+ cells are able to specifically recognize and kill allogeneic cells (Matis 1987, Ciccone 1988b). In our laboratory it has been demonstrated that TCR gamma/delta+ cells were able to recognize allogeneic cells in conventional MLC. Both proliferation and lysis of target cells bearing the stimulating alloantigens could be detected (Ciccone 1988b). This phenomenon was clearly specific since neither autologous nor allogeneic unrelated blasts were lysed. The same responding population cultured with autologous irradiated cells did not lyse either autologous or allogeneic target blast cells. An additional demonstration that TCR gamma/delta+ cells can recognize allogeneic cells was obtained by the analysis of MLC-derived T-cell clones (Ciccone 1988a). Clones that specifically lysed allogeneic target cells did not lyse autologous or unrelated blasts. In addition they were either BB3+ or A13+ (see Table I), thus, indicating that both types of TCR gamma/delta can mediate alloantigen recognition. The analysis of allospecific cell clones also provided direct evidence that the specific cytolytic activity is not necessarily correlated with the expression of MHC-unrestricted cytotoxicity. |
