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The leucocyte common antigen, CD45 (T200, Ly-5), exists in a number of isoforms generated by differential usage of three exons that code for an extracellular region close to the NH2 terminus. Use of antibodies to different isoforms of CD45 has lead to the identification of two subsets of CD4+ T cells in rat, man and mouse. Data on the functions of the two rat CD4+ T-cell subsets isolated on the basis of different levels of expression of exon B (and/or C) are largely concordant with those obtained from the two subsets of human CD4 + T cells defined by their levels of expression of exon A. However, results presented in this paper on the CD45 phenotype of rat T cells that produce interferon-gamma (IFN-γ) are not compatible with the human data, if it is assumed that there are only two functional subsets of CD4+ T cells. The data could, in principle, be reconciled if the expression of exons A and B defined three rather than two subsets, and this possibility has now been examined in man where monoclonal antibodies against both A and B exon products are available. The results show the presence of a third CD4+ T-cell subset and that this extra subset is contained within the population originally shown to provide memory T-cell function. [ABSTRACT FROM AUTHOR]