CD7 and CD57 are two cell surface molecules related to the differentiation or functional stages of CD4+ T cells. The CD4+CD7- T cells represent a minor subset of CD4+ cells in normal individuals and are considered to contain the normal counterpart of Sezary T cells; the CD4+CD57+ peripheral blood lymphocytes (PBL) are detectable in long- term renal allograft recipients. We compared the cell surface expression of these CD7 and CD57 markers on CD4+ T lymphocytes in peripheral blood and lymphoid organs from normal individuals and human immunodeficiency virus (HIV)-infected patients. Our results indicate that CD4+CD7- T cells in normal PBL do not express CD57 and were poorly responsive to anti-CD3 monoclonal antibody (MoAb), the activation being restored by addition of anti-CD28 MoAb. This CD4+CD7- cell subset is increased in peripheral blood during HIV infection, and its progressive expansion mirrors both the absolute and relative decrease of CD4+ T cells. The lack of CD7 expression is correlated with CD57 acquisition on CD4+ T cells because CD4+CD7-CD57+ cells represent a major component of the CD4+CD7- subset in HIV-infected patients. Our results suggest that the presence and the expansion of CD4+CD7-CD57+ T lymphocytes, which do not behave as previously defined helper subsets, may participate to the immune dysfunction observed during HIV infection.

In this study, we have investigated the ability of various cytokines to induce the maturation of acute lymphoblastic leukemia (T-ALL) cells with early T-cell phenotype. Leukemic blasts from 17 untreated T-ALL patients were assayed for their ability to acquire mature T-cell markers, CD3/T-cell receptor (TCR) in particular, after incubation with one or a combination of recombinant human interleukin-1 (IL-1), IL-2, IL-4, IL-7, and CD2-specific monoclonal antibody (MoAb). IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells. Differentiation of T-ALL cells was also evidenced through the downregulation of CD34 precursor cell antigen, the generation of CD4+ and CD8+ cells from CD4+ CD8+ precursors, and the acquisition of mature T-cell functions. CD2 ligation induced a progressive increase of surface expression of IL-2 receptor alpha (IL- 2R alpha) and IL-2R beta and an accelerated in vitro death of leukemic cells. The ligation of IL-2R by IL-2 rescued T-ALL cells from death and promoted their progression toward more mature cells expressing extracellular CD3/TCR alpha beta complexes. Intracellular analysis indicates that TCR alpha transcription and membrane translocation of both TCR alpha and TCR beta were promoted in these conditions. Analysis of intracellular signals transduced during T-ALL differentiation indicated that CD2-ligation induced Ca2+ influx and that the ligation of CD2 and IL-2R induced distinct tyrosine phosphorylation patterns. The addition of inhibitors of tyrosine phosphorylation abolished T-ALL cell differentiation, which suggests the involvement of tyrosine kinases in this phenomenon. Together, we showed the constant maturation of leukemic early T cells after stimulation of surface CD2 and the high- affinity IL-2R.

4939 Background: PIOL is a very rare subset of non Hodgkin lymphoma, usually arising in elderly patients and characterized by a high level of relapse, mainly in the first year, with more than 10 of cases relapsing in brain, and a short survival. There is no consensus on treatment procedures, even in first line, and prospective comparative studies do not exist. Classical attitudes are systemic chemotherapy (SC), often high dose methotrexate, radiotherapy or intraocular injection of methotrexate (IM) but publication on R/R PIOL are exceptional. New treatments are necessary, especially with a good tolerance profile. As Temozolomide (Te) hassome efficiency on primary-central-nervous-system lymphoma (PCNSL) we used this drug in R/R PIOL in our center. Methods: Inclusion criteria were a diagnosis established on cytological and molecular analysis after vitrectomy or anterior chamber puncture, and the absence of brain or meningeal localization. Treatment consisted in Te at 150mg/m2orally 5 days per month, without corticosteroid use, in absence of any response, dosage was increased to 200mg/m2. A complete response was defined as a normalization of eye exam and intraocular interleukins 10 and 6. Results: Six patients were analyzed, 2 males and 4females, mean age 70 years \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{49}{82}.\) \end{document}. All received systemic chemotherapy with at least high dose methotrexate and high dose cytarabin before Te, five were in second line and one in third, after autologous hemopoietic stem cells transplantation (ASCT) conditioned by thiotepa, cyclophosphamide and busulfan. Mean response duration before Te was 241 days \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{23}{524}.\) \end{document}. All but one received Te in monotherapy, one having an association with ifosfamid followed by ASCT. CR has been obtained in 3 patients, PR in one, progressive disease in two. One of the 3 patients in CR stopped Te by himself after three months, relapsed two months later and is again in CR after reintroduction of Te. CR patients are still disease free at 42, 190 and 878 days; two of these patents described a clear improvement of their vision as soon as one or two weeks after Te introduction. Overall survival for the six patients, from day 1 of Te is 313 days \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{101}{1001}.\) \end{document} No grade 3/4 toxicity has been described. Conclusion: This study describe for the first time use of Te in PIOL, and in this very rare disease, it represents significant series. Te appears as a safe and efficient treatment of R/R PIOL, even after high dose chemotherapy and/or in elderly patients. Longer follow-up and larger studies are necessary to confirm these data. Disclosures: No relevant conflicts of interest to declare.