RESUMO
Since the earliest days of the HIV epidemic, the number of CD4(+) T cells per unit volume of blood has been recognized as a major prognostic factor for the development of AIDS in persons with HIV infection. It has also been generally accepted that approximately 2% of total body lymphocytes circulate in the blood. In the present study, we have used a nondepleting humanized anti-CD4 monoclonal antibody labeled with the gamma emitter indium-111 to visualize the CD4(+) T-cell pool in vivo in nonhuman primates with simian HIV infection. A strong correlation was noted between radiotracer uptake in spleen, tonsil, axillary lymph nodes, and peripheral blood CD4 T-cell counts (rho = 0.75, 0.93, and 0.85, respectively, P < .005). The relationship between radiotracer retention in lymphoid tissues and CD4(+) T-cell counts in the circulation was governed by an exponential law. These data provide an estimate for the total number of lymphocytes in the body as being between 1.9 and 2.9 x 10(12) and suggest that the partition between peripheral blood and lymphoid tissue is between 0.3% and 0.5%.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD4/imunologia , Linfócitos T CD4-Positivos/patologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Imunoglobulina G/imunologia , Macaca mulatta , Masculino , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome de Imunodeficiência Adquirida dos Símios/radioterapia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Especificidade por Substrato , TomografiaRESUMO
The identification of antiretroviral drugs that prevent, or delay for extended periods, progression of HIV-related disease has been of limited success. Because the number of HIV-infected people continues to increase, other therapeutic approaches must be tested. Using simian immunodeficiency virus (SIV)-infected macaques in a feasibility study, total lymphoid irradiation (TLI) was administered in fractionated doses to the supradiaphragmatic and then the infradiaphragmatic lymph nodes until a cumulative dose of 34.2 Gy was achieved in each field. During treatment and for more than 1 year of follow-up, the effects of TLI on various virological, hematological, and immunological parameters were evaluated and compared to those of similarly treated, uninfected macaques. Despite sustained low numbers of CD4+ lymphocytes (< 100/microliters blood) during treatment, TLI was well tolerated, did not result in intercurrent infections, and more importantly, induced a transient decrease in viral burden and did not exacerbate disease. Remarkably, this lack of disease progression and apparent containment of SIV replication were maintained despite persistent failure of PBMCs to respond to mitogen stimulation. Because SIV (and HIV) requires activated lymphocytes to replicate, failure of PBMCs to respond fully to stimuli may have contributed to restricting virus replication. This idea was supported by in vitro experiments in which infection of PBMCs before TLI produced higher levels of cell-free SIV than those obtained during or after TLI. Last, repopulation of peripheral blood and lymph nodes with lymphocytes paralleled that observed in uninfected control animals. The results indicate that (1) immunosuppression alone is not sufficient to induce progression to AIDS, (2) SIV infection does not undermine the ability of the immune system to regenerate new cells during the clinically latent phase, and (3) further evaluation of TLI or other immunosuppressive regimens as potential therapies for HIV disease is warranted.