Anti-Lair1 Monoclonal antibody, clone 224 [PE]

Purpose: A global gene expression microarray analysis of surplus chorionic villus sampling (CVS) tissues identified leukocyte-associated immunoglobulin-like receptor 2 (LAIR2) as down-regulated in the first trimester of pregnancies destined for preeclampsia. Neither the localization nor the function of LAIR2 has been examined in the placenta. Localization studies were conducted in placental tissues to determine the precise sites of LAIR2 mRNA production and protein binding. Results: Quantitative real time polymerase chain reaction (qRT-PCR) indicated LAIR2 expression in CVS, but none in breast, lymph node, kidney, skin, uterus, or third trimester placentas. In situ hybridization (ISH) revealed a highly restricted LAIR2 localization. LAIR2 mRNA was found only in the more distal portions of trophoblast anchoring cell columns, adjacent to the invading extravillous trophoblast (EVT). Immunohistochemistry (IHC) detected intracellular LAIR2 staining in these same cells. Extracellular staining of this soluble receptor was found in the acellular material between invasive EVT cells distal to the anchoring cell columns. Conclusions: ISH and IHC staining for LAIR2 detected specific, highly localized expression at the leading edge of EVT anchoring cell columns in first trimester placentas. This staining likely identifies the site of production for this soluble receptor. Following secretion, the receptor appears to bind extracellular material among the invasive EVT. The precise restriction of this protein only to the sites of EVT invasion strongly suggests that it functions to regulate this invasion. The decreased LAIR2 expression noted in first trimester placentas that ultimately developed preeclampsia further suggests that alterations in LAIR2 may play an etiologic role in preeclampsia. (C) 2010 Elsevier Ltd. All rights reserved.

Objective: CD70 molecules expressed by activated T cells provide potent B cell stimulatory signals. We hypothesized that an altered CD70 expression might contribute to B cell abnormalities during HIV-1 infection. Design: CD70 expression and the functional and migratory properties of the CD4(+)CD70(+) T lymphocytes were analyzed in HIV-1-infected patients and in humanized mice. Correlations were tested between CD70 expression and features of B-cell activation, apoptosis sensitivity and functional exhaustion. Methods: CD4(+)CD70(+) T cells were analyzed in cohorts of CD4(+) T-cell lymphopenic, viremic or nonlymphopenic, nonviremic HIV-1-infected patients and in noninfected individuals. CD70 upregulation was also followed in HIV-1-infected humanized mice. CD38, CD95, LAIR1 and PD-1 expressions were monitored on B-cell subpopulations, Ki67 was assessed to estimate B-cell proliferation and antibody levels were measured in plasma. Results: Blood CD4(+)CD70(+) T-cell frequencies increased in response to CD4(+) T-cell depletion or high viremia levels as a possible consequence of increased activation and proliferation in this subset. CD4(+)CD70(+) T cells produced T-helper 1-type cytokines and expressed chemokine receptors mobilizing toward sites of inflammation but not to lymphoid follicles. High CD70 expression was observed in HIV-1-infected humanized mice at extrafollicular sites (peritoneum, bone-marrow). CD4(+)CD70(+) T-cell frequencies correlated with the expression of the activation marker CD38 and the death receptor CD95 on various memory B-cell subsets, with B-cell proliferation and with plasma IgG levels. Conclusions: CD4(+)CD70(+) T cells may contribute to B cell hyperactivation and accelerated memory B-cell turnover during HIV-1 infection. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.