Mohan N. Viswanathan

Loss of Cytomegalovirus-Specific CD4+ T Cell Responses in Human Immunodeficiency Virus Type 1–Infected Patients with High CD4+ T Cell Counts and Recurrent Retinitis

Clinical histories are reported for 2 patients treated with highly active antiretroviral therapy (HAART) who experienced multiple relapses of cytomegalovirus (CMV) retinitis, despite suppression of human immunodeficiency virus type 1 (HIV-1) viremia and improvement in CD4+ T cell counts (to >400 cells/microL). CMV-specific CD4+ T cell immune reconstitution was measured directly, using cytokine flow cytometry, which revealed persistent deficits in CMV-specific CD4+ T cell responses in both patients. CMV-specific T cells constituted 0.14% and 0.05% of the total CD4+ T cell count in these patients, which is significantly lower than the percentages for 34 control subjects (0.6%-46%; CD4+ T cell count range, 7-1039 cells/microL; P=.019). Deficits in pathogen-specific immune responses may persist in some individuals, despite suppression of HIV-1 replication and substantial increases in circulating CD4+ T cells after HAART, and such deficits may be associated with significant morbidity from opportunistic infections.

Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy.

We compared therapeutic benefits of intramyocardial injection of unfractionated bone marrow cells (BMCs) versus BMC extract as treatments for myocardial infarction (MI), using closed-chest ultrasound-guided injection at a clinically relevant time post-MI. MI was induced in mice and the animals treated at day 3 with either: (i) BMCs from green fluorescent protein (GFP)-expressing mice (n = 14), (ii) BMC extract (n = 14), or (iii) saline control (n = 14). Six animals per group were used for histology at day 6 and the rest followed to day 28 for functional analysis. Ejection fraction was similarly improved in the BMC and extract groups versus control (40.6 +/- 3.4 and 39.1 +/- 2.9% versus 33.2 +/- 5.0%, P < 0.05) with smaller scar sizes. At day 6 but not day 28, both therapies led to significantly higher capillary area and number of arterioles versus control. At day 6, BMCs increased the number of cycling cardiomyocytes (CMs) versus control whereas extract therapy resulted in significant reduction in the number of apoptotic CMs at the border zone (BZ) versus control. Intracellular components within BMCs can enhance vascularity, reduce infarct size, improve cardiac function, and influence CM apoptosis and cycling early after therapy following MI. Intact cells are not necessary and death of implanted cells may be a major component of the benefit.

453. Injectionof Different Adult Cell Types into Mouse Myocardium Three Days after Myocardial Infarction Using a Novel Echo-Guided Technique Improves Cardiac Function

Objective: Myocardial regeneration based on stem cell transplantation has emerged as a potential therapeutic approach toward replacing myocardial scar with functioning contractile tissue after myocardial infarction (MI). Considerable interest has focused on bone marrow cells (BMCs) and endothelial progenitor cells (EPCs) because they appear successful in attenuating remodeling following acute MI. However, preclinical experiments toward this goal have been limited to treatment within hours of an MI, in contrast to human trials, in which cell treatment has been performed several days later after patient stabilization and autologous cell harvesting. We sought to compare the therapeutic effects of different types of putative stem and progenitor cells in a mouse model of MI using a novel closed-chest echo-guided injection approach to deliver cells 3 days after infarction.