Since activated macrophages and cytokines are found in human milk (HM), a flow cytometry study was conducted to determine whether T cells in HM display phenotypic markers of recent or previous activation. HM was collected during the first 3 d of lactation. The Paint-a-Gate program was used to optimize gating on the lymphocyte population. A mean & 1 SD of 4 & 3% of total HM leukocytes were lymphocytes and 96 f 3% were macrophages and granulocytes (N = 33 subjects). HM lymphocyte populations were further analyzed in five subjects. T cells (CD3+) represented 83 f 11% and B cells (CD19') were 6 & 4% of HM lymphocytes. The mean CDWCDB ratio of T cells in HM was 0.88 (range 0.40-1.25). This ratio was significantly decreased compared to the peripheral blood (PB) of control adults (P < 0.02) and postpartum women (P < 0.021, due mostly to a significant increase in CD8+ CD3+ cells in HM compared to the PB of control adults (P < 0.002) and postpartum women (P < 0.05). T cells bearing markers of recent activation were significantly increased in HM compared to the PB of control adults: 85 f 7% of CD3+ cells in HM were HLA-DR+ (controls, 10 f : 4%; P < 0.001), and 15 k 6% of CD3+ cells in HM were IL-2R+ (controls, 6 f 2%; P < 0.001). Subpopulations of CD4+ and CD8+ cells in HM defined by the T200 isoforms CD45RA and CD45RO were markedly altered compared to PB, indicating a striking shift from virginal to antigen-primed (memory) T cells in HM and suggesting certain functional capacities for these cells. Virtually all CD4+ cells (99.8 2 0.4%) and 92 f 5% of CDB+ cells in HM were CD45RO+ (vs. 71 f 12% and 50 f lo%, respectively, in the PB of postpartum women; P < 0.001). CD4+ and CD8+ cells expressing CD45RA were correspondingly markedly reduced (P < 0.001). This phenotypic pattern of T cells in HM may result from T cell activating substances in HM and/or selective homing of T cells to the breast. Conversely, activated T cells in HM may be responsible for cytokines in HM. These activated and memory T cell populations may be transferred to the infant via breastfeeding.Key terms: Human milk immunology, T lymphocyte subsets, flow cytometry, markers of activation, leukocyte common antigen isoforms It has been known for some years that leukocytes are part of the immunologic system in human milk (HM) (42,121. About 3 million leukocytes are found in each milliliter of HM produced during the first few days postpartum, and the principal types of leukocytes found in HM during that period are neutrophils (40-60%), macrophages (30-50%), and lymphocytes (5-9%). T cells comprise 60-73% of HM lymphocytes based on the capacity to form rosettes with sheep erythrocytes [12,34], and the thermostability of these rosettes suggests that HM T cells are activated [341. The

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A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders. (J.

Eleven patients with mature or peripheral T-cell lymphoma (PTL), other than mycosis fungoides, were identified using an extensive battery of T- and B-cell markers. Eight cases had a histologic diagnosis of either diffuse large cell or mixed lymphoma, three of small cell type. All cases had one or more "mature" T-antigens and an absence of B- and immature T-antigens. Assessment of T-antigens included E-rosettes (Er), anti-Leu 1-7 and Tdt. The authors delineated striking heterogeneity of T-antigen expression: 9 different immunotypes in 11 cases. Subset T-antigen assessment indicated T-helper neoplastic cells in five cases and T-suppressor in two. The remaining four had universal T-antigens alone. Seven cases appeared to have "novel" T-phenotypes not corresponding to normal T-ontogeny phenotypes. Novel or idiosyncratic phenotypes may be a key characteristic of PTL. Since no single T-antigen, including Er and Er receptor (Leu-5), was expressed in all cases, a battery of monoclonal antibodies is necessary to detect PTL. Clinically, the authors found PTL unexpectedly aggressive, despite mature immunotype. Most patients were elderly (median age 69); all had extranodal disease with cutaneous involvement (six cases) most frequent. Responses to chemotherapy frequently proved transient, with median survival of nine months. A fulminant course was noted even with localized presentation. Clinical outcome suggests PTL requires new therapeutic strategies.

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Costs determined for university medical centers in the United States. Results showed that, at the median cohort age of 52, IFN add 9.9 quality-adjusted months at an added cost of $13,900 (marginal cost-effectiveness of $16,900 per quality-adjusted life year, or QALY). A more complex, two-stage model approximates the actual cohort survival curves much better than a simple, one-stage model, but both models yield essentially the same marginal cost-effectiveness. Sensitivity analysis to quality of life on IFN shows marginal cost-effectiveness ranging from $15,200/QALY (no penalty for IFN) to $21,300/QALY (20% quality adjustment, greater than that reported). The model is quite insensitive to the probability of IFN toxicity. The model is moderately sensitive to the efficacy of IFN in delaying progression, particularly in the first 18 months (pProgI), but the marginal cost-effectiveness does not rise to $50,000/QALY until pProgI increases 220% from the baseline. Although the model is moderately sensitive to the cost of IFN (cIFN), marginal cost-effectiveness is below $50,000/QALY for values of cIFN below $2580/month (baseline cIFN = $850/month, corresponding to a marginal cost-effectiveness of $16,900/QALY in the baseline case). If the model is modified to reflect the 14% overall survival advantage at five years found in trials utilizing more intensive initial chemotherapy (including the GELF trial), then the marginal cost-effectiveness drops to $11,900/QALY in the baseline case. In condusion, based on data from the GELF study, low-dose interferon alfa-2b is cost-effective when added to CHVP therapy in the treatment of high-tumor-burden follicular non-Hodgkin's lymphoma. The analysis is robust: the model employs very conservative assumptions, and additive IFN remains cost-effective over wide ranges of variables in sensitivity analyses. The marginal cost-effectiveness is best expressed as being in the range of $12,000/QALY to $17,000/QALY in the baseline case. A simple Markov model can be used to describe treatment regimens with distinct periods of therapy.

We have achieved a comprehensive immunotopographic mapping of human thymus by using a large battery of monoclonal antibodies and the methodological refinement of comparative serial tissue section immunohistochemistry, allowing analysis of multiple phenotypes in the same tissue site. Previous immunohistochemical studies of thymus have concentrated on the majority T-cell and epithelial cell populations. Besides demonstrating the complexity of T-cell antigenic expression (e.g., simultaneous cortical expression of Leu 2, Leu 3, CALLA, Tdt, and Leu 6), we delineate surprisingly complex B-cell zones (e.g., septal B-follicles with DRC+C3d+ dendritic cells and zonal maturation of B-cells). Whereas septal B-follicles were found in 25% of cases, medullary B-cells were universally present as a substantial minority component. This expanded immunotopographic knowledge of the complex T-, B-, epithelial, and reticulum cell neighborhoods suggests that the thymus is an organ capable of a broad repertoire of immunological responses, not limited to T-cell development.