HYALURONAN-BINDING FUNCTION OF CD44 IS TRANSIENTLY ACTIVATED ON T-CELLS DURING AN IN-VIVO IMMUNE-RESPONSE

Though CD44 functions as a cell surface receptor for hyaluronan (HA) i n some cell lines, most normal hematopoietic cells expressing CD44 do not bind HB. Certain CD44-specific monoclonal antibodies (mAbs) can ra pidly induce CD44-mediated HA binding in normal murine T cells. This o bservation suggests that in vivo mechanisms may exist for activating t he HA receptor function of CD44 on normal T cells. Here, it is shown t hat up to one third of splenic T cells are capable of CD44-mediated bi nding of fluorescein-conjugated HA (Fl-HA) during an in vivo allogenei c response. HA binding activity peaks at 7-8 d postinjection and decli nes rapidly. These rapid kinetics could be the result of transient act ivation of CD44 function and/or differentiation or expansion of short- lived population(s) that have constitutive HA-binding function. Both C D4 and CD8 T cells are included in the HA binding population which is strongly CD44 positive. After separation of HA-binding cells from nonb inding cells by cell sorting, it is shown that almost all cytotoxic ef fector cells are found in the HA-binding population. However, there is no evidence that CD44-mediated HA recognition is directly involved in the killing of target cells, since cytotoxicity could not be inhibite d by CD44-specific mAbs that inhibit HA binding or by soluble HA, PCR amplification of cDNA reverse transcribed from RNA of sorted HA-bindin g cells indicated no evidence for CD44 isoforms other than the standar d (hematopoietic) form. Though CD44 expression is known to be elevated upon T cell activation, and, as shown here, HA-binding function is in duced in a portion of CD44-expressing T cells including cytotoxic effe ctor cells, the role of CD44 and HA-recognition in immune responses is not known.