Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function

Abstract

Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.

Thymic Function during 12 Months of Highly Active Antiretroviral Therapy in Thai HIV-Infected Patients with Normal and Slow Immune Recovery

“…Although the criterion for poor immune response in our study and the study by Teixeira et al (19) were similar, the poor immune responders in the latter were older than those in our study (38 versus 46 years). Thymic size and function reportedly decrease with age (6); therefore, older age may have contributed, in part, to the impaired thymic output found in poor immune responders in the study by Teixeira et al (19).…”

“…Therefore, compared with our study, these 2 previous studies evaluated thymic function during different periods after HAART. In addition, the patient characteristics were different: the poor immune responders in the study by Benveniste et al (18) were patients with CD4 ＋ T-cell counts of ＜250 cells/mL after 12 months of HAART, whereas those in the study by Teixeira et al (19) and in the present study were patients with CD4 ＋ T-cell count increases of ＜100 cells/mL after 12 months and 6 months of HAART, respectively. Although the criterion for poor immune response in our study and the study by Teixeira et al (19) were similar, the poor immune responders in the latter were older than those in our study (38 versus 46 years).…”

“…In addition, the patient characteristics were different: the poor immune responders in the study by Benveniste et al (18) were patients with CD4 ＋ T-cell counts of ＜250 cells/mL after 12 months of HAART, whereas those in the study by Teixeira et al (19) and in the present study were patients with CD4 ＋ T-cell count increases of ＜100 cells/mL after 12 months and 6 months of HAART, respectively. Although the criterion for poor immune response in our study and the study by Teixeira et al (19) were similar, the poor immune responders in the latter were older than those in our study (38 versus 46 years). Thymic size and function reportedly decrease with age (6); therefore, older age may have contributed, in part, to the impaired thymic output found in poor immune responders in the study by Teixeira et al (19).…”

Restoration of the CD4 T Cell Compartment after Long-Term Highly Active Antiretroviral Therapy without Phenotypical Signs of Accelerated Immunological Aging

“…However, because T cell proliferation declines after HAART initiation even though the CD4 T cell compartment is still very much depleted (19,23), it can be argued that residual activation rather than a homeostatic response drives T cell proliferation during HAART. In addition, the observations that low TREC contents (10 -12, 16, 24, 25), short telomeres (10), and high levels of activated CD38 ϩ HLA-DR ϩ T cells (12,19,20,26,27) and proliferating (Ki67 ϩ ) naive CD4 and CD8 T cells (27) are related to poor CD4 T cell reconstitution support the notion that residual activation causes the increased levels of T cell proliferation.…”

Interleukin-7 and Immunorestoration in HIV: Beyond the Thymus

“…Indeed, in HIV infection, there is clinical evidence that the nadir of the CD4 count may be predictive of overall immune competence following HAART-induced immune reconstitution, illustrating that expansion of a very limited repertoire is only of marginal benefit (6,7). These features of thymic-dependent and thymic-independent pathways to T cell regeneration lead to the prediction that the degree of immune competence in a host depends, at least to some degree, on the extent to which of thymic function can be restored (8). As discussed elsewhere in this issue, strategies directed at enhancing immune reconstitution following initiation of highly active antiretroviral therapy (HAART) have been a major area of recent investigation.…”