CD45RC ISOFORMS DEFINE 2 TYPES OF CD4 MEMORY T-CELLS, ONE OF WHICH DEPENDS ON PERSISTING ANTIGEN

The cellular basis of immunological memory remains a controversial are a with respect to the identity of memory T cells and the role of persi sting antigen. CD4 T cells are phenotypically divided by the expressio n of high and low molecular weight isoforms of CD45, surface markers t hat are frequently used to identify ''naive'' (CD45R(high)) and ''memo ry'' (CD45R(low)) subsets. The latter subset responds rapidly in antig en recall assays but paradoxically has a short life span, a property t hat is difficult to reconcile with long-term memory. The present study examines these issues using a DTH (delayed-type hypersensitivity) mod el in which contact sensitivity to dinitrochlorobenzene (DNCB) was tra nsferred to athymic nude rats by recirculating CD4 T cell subsets defi ned in the rat by the anti-CD45RC mAb OX22. As expected, CD45RC(+) (bu t not RC(-)) CD4 T cells from normal unprimed rats transferred a DNCB- specific DTH response, whereas, 4 d after sensitization the CD45R C- ( memory) subset alone contained the DNCB reactivity. However, when dono r cells were collected from thymectomized rats sensitized two mo earli er, DNCB-specific responses were transferred by both CD45RC(-) and RC( +) subsets suggesting that many of the latter had developed from cells with a memory phenotype. This was confirmed when CD45RC(-) CD4 T cell s from 4-d primed rats were parked in intermediate nude recipients and recovered 2 mo later. DNCB-specific activity was now found wholly wit hin the CD451RC(+) ''revertant'' subset; the CD45RC(-) CD4 T cell popu lation was devoid of activity. importantly, we found that the total sw itch-back from CD45RC(-) to RC(+) could be prevented, apparently by pe rsisting antigen. The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45R(low) type which orchestrates the rapid kinetics, the other, a longer-lived CD45R(high) revertant which ensures that immunological memory endures.