Unique cell surface phenotypes of proliferating lymphocytes in mice homozygous for lpr and gld mutations, defined by monoclonal antibodies to MRL/Mp- lpr/lpr T cells

Abstract

In mice bearing the autosomal recessive gene of either lpr or gld, generalized T-cell proliferation and autoimmunity occurs. The surface antigen profiles of these proliferating cells were analyzed using two-color flow cytometry analysis with two newly established rat monoclonal antibodies (ALP-1, ALP-2) directed to lpr cells. The Lp-1 antigen, denned by ALP-1, is expressed exclusively on approximately one-half of proliferating lpr and gld lymph node cells. The Lp-2 antigen, like B 220, is expressed on 80–90% of lpr and gld lymph node cells, the cells in B-cell lineage and a small population of Ly-2 + T cells from normal mice. Thus, the lpr and gld lymph node cells were classified into three subsets, Lp-1 +/Lp-2 +, Lp-1 −/Lp-2 + and Lp-1 −/Lp-2 −. After stimulation with Con A or a combination of IL-2 and phorbol ester, a small population of T cells from normal mice became Lp-1 +. The same treatment increased Lp-2 +/Ly-2 + and induced Lp-2 +/L3T4 + T-cell populations. Therefore, it seems likely that these phenotypically unique T cells are generated at some stage during the proliferation and differentiation of certain normal T-cell subpopulations. The aberrant T cells in mice with lpr and gld mutations may even be normal regulatory T cells, if they are not proliferating abnormally.