Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.

The human Ia-like antigens were recognized initially as a series of HLA-linked alloantigens primarily represented on B lymphocytes with multiple pregnancy sera (I). Later, they were detected by hetero-antisera raised against the isolated protein from cell membranes (2-4). In addition to their presence on B cells and monocytes, they have been detected on the leukemic blast in eases of acute lymphocytic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia in blastic crisis (4-6). Recently, these Ia antigens were also shown to be present on the surface of precursor cells responsible for colony formation of both the myeloid monocytic and erythroid series (7-9) and on the surface of nonblood cells such as epidermal Langerhans cells (10).The presence of certain types of Ia antigens on T lymphoeytes has been demonstrated in murine systems, although the exact molecular character remains unclear (11). The presence of Ia antigens on human T cells has not been well documented. The present studies demonstrate the presence of Ia antigens on a small population of normal circulating human T lymphocytes, on T lymphocytes grown in long-term cultures, and on certain leukemic T cells. Evidence also is presented showing that cells responsible for the generation of helper activity during a mixed lymphocyte reaction are contained in this Ia-bearing T-cell population. Materials and MethodsIsolation of Lymphocytes. Mononuclear cells from the peripheral blood of normal individuals and patients with leukemia and various lymphoproliferative states and tonsillar mononuclear cells were isolated as described previously (12). Spontaneous rosette formation between human lymphocytes and sheep erythrocytes (SRBC) were performed with neuraminidase-treated SRBC (E). The rosette-forming cells (E-RFC) were separated from the nonrosette-forming cells by Ficoll-Hypaque (Pharmacia Fine Chemicals, Div. of Pharmacia Inc., Piscataway, N. J.) gradient centrifugation. The RFC-enriched fraction was purified further by repeated gradients until no significant numbers of cells were observed at the interphase. The E-RFCs were recovered after lysis of SRBC by a Tris-buffered ammonium chloride solution. Tonsillar B cells were obtained by the depletion of E-RFCs from the mononuclear cell preparations.