FUNCTIONAL CD4(-CELL SUBSETS DEFINED BY EXPRESSION OF CD45RC AND NTA260 ANTIGENS AND AGE-ASSOCIATED POLARIZATION IN MURINE LUPUS() T)

Using two mAb, one specific to the alternative exon 6-dependent epitop e of CD45 molecules (JH6.2) and one a natural thymocytotoxic autoantib ody (NTA) with an unknown reactive epitope (NTA260), we subdivided spl enic CD4(+) T cells from 2-month-old BALB/c mice into five phenotypica lly distinct subsets. CD45RC(+)NTA260(-) (S I) cells were phenotypical ly analogous to CD4(+) T cells predominating in newborn mice and produ ced a significant amount of IL-2, but not so IL-4, IL-10 or IFN-gamma when stimulated with immobilized anti-CD3 mAb in vitro. They appeared to consist mainly of naive ThP cells. The CD45RC(+)NTA260(+) (S II) su bset also produced IL-2, but not other cytokines; however, the IL-2 le vels produced were much higher than seen with the S I subset, thereby suggesting the predominance of further maturated ThP cells. The CD45RC (-)NTA260(+) (S III) subset mainly produced IL-4, IL-10, IFN-gamma and less IL-2, and contained memory cells that helped the secondary antib ody response to a recall antigen, and hence contained T(h)2 and probab ly a mixture of T(h)0 and T(h)1 cells. The CD45RC(-)NTA260(-) (S IV) s ubset was a poor responder to the immobilized anti-CD3 mAb. The CD45RC (bright)NTA260(dull) (S V) subset consisted of a small number of cells that were phenotypically analogous to activated CD4(+) T cells. While an age-associated decrease in the proportion of S I and less markedly in S II and in turn increase in S III subsets of CD4(+) T cells occur red in normal BALB/c mice, autoimmune disease-prone (NZBxNZW)F-1 mice showed a marked age-associated decrease in the proportion of not only S I, II but also III subsets. As aged (NZBxNZW)F-1 mice carry CD4(+) T helper cells for IgG anti-DNA antibody production, such age-associate d polarization to the S IV subset appears to be critical in the pathog enesis of autoimmune disease in these mice.