Human CD4+CD45RO+ and CD4+CD45RA+
T cells synergize in response to alloantigens* Alloantigens, unlike recall antigens, activate both CD45RA+ (naive) and CD45RO+ (memory) CD4+ cells to the same extent. These Tcell subsets may therefore interact with each other in response to alloantigens on transplanted grafts. We have investigated if the ability of activated CD4+CD45RA+ and CD4+CD45RO+ Tcells to produce and respond to interleukin 2 (IL2) and IL4 may be involved in this interaction. After activation, both subsets up-regulate their IL2 receptor (IL2R) and IL4R expression, yet IL4 substantially enhanced the proliferation of the CD4+CD45RA+ but not of the CD4+CD45RO+ Tcell subset, while IL 2 increased the proliferation of CD4+CD45RO+ but not of the CD4+CD45RA+ T cells. Significantly, the CD4+CD45RA+ T cells synthesized two-to threefold more mRNA for IL2 than the CD4+CD45RO+ subset, while the CD4+CD45RO+ T cells synthesized mRNA for IL 4 and interferon-y exclusively. The addition of IL2 to alloactivated CD4+CD45RO+ T cells further up-regulated their production of all three lymphokine mRNA; in contrast, IL4 induced an increase in mRNA for IL 2 in only the alloactivated CD4+CD45RA+ subset. The reciprocity in the ability of both these CD4+ Tcells to synthesize and respond to L 2 and IL4 may provide a rationale for the regulation of lymphokine interactions in vivo. Furthermore, the synergy between these subsets in response to alloantigens, which was directly quantitated by co-culturing CD4+CD45RA+ and CD4+CD45RO+ cells together prior to activation, may potentiate the alloreactivity against transplanted grafts in vivo.
* This work was funded by grants from Sandoz Pharma Ltd. and also the Arthritis and Rheumatism Council.