T-lymphocyte heterogeneity in the rat: separation of distinct rat T-lymphocyte populations which respond in syngeneic and allogeneic mixed lymphocyte reactions.

These experiments were designed to determine if separate subpopulations of T cells were involved in the syngeneic and allogeneic mixed lymphocyte reaction. Rat lymph node T cells were separated into W3/25+ and W3/25- subpopulations by panning with the monoclonal antibody W3/25 and tested for their ability to proliferate in both syngeneic (SMLR) and allogeneic (MLR) mixed lymphocyte responses, as well as to develop cytotoxicity against allogeneic, syngeneic, and trinitrophenol (TNP)-modified syngeneic targets. The W3/25+ T cells reacted strongly in the SMLR and the MLR whereas the W3/25- fraction proliferated only in response to allogeneic stimulation and with a kinetic pattern distinct from W3/25+. Furthermore, addition of W3/25 monoclonal antibody directly to the cultures was shown only to inhibit the proliferation of the W3/25+ T-cell fraction. The W3/25- subpopulation contained cytotoxic T cells (CTLs) against both allogeneic determinants and TNP-modified self. However the requirements for the activation of allospecific CTLs were distinct from those for CTLs for TNP-self in that W3/25- allospecific CTLs required no detectable help from W3/25+ T cells but generation of the CTL response against TNP-self required the presence of W3/25+ helper T cells (Th). These data suggest that in the rat, there exist subsets of T cells recognized by their cell surface phenotype that distinguish between self and nonself determinants and the requirements for activation are different for each of these populations.