Interleukin‐2 Increases CD4⁺Lymphocyte Numbers but Does Not Enhance Responses to Immunization: Results of A5046s

Abstract

To ascertain whether CD4(+) lymphocyte increases induced by interleukin (IL)-2 enhanced in vivo immune responses, 38 human immunodeficiency virus (HIV)-infected patients who had received highly active antiretroviral therapy (HAART) or HAART and IL-2 for at least 60 weeks were immunized with tetanus toxoid, inactivated glycoprotein 120-depleted HIV-1, and hepatitis A and B vaccines. Despite dramatic increases in CD4(+) lymphocyte counts, IL-2 did not enhance immunization responses.

Treatment with Recombinant Growth Hormone Is Associated with Modest Improvement in CD4 Lymphocyte Reconstitution in HIV-Infected Persons on Antiretroviral Therapy: Results of ACTG A5174

“…However, other interventions such as IL-2, which were associated with significant CD4 þ lymphocyte increases over ART alone, did not consistently lead to improved vaccine responses as measured by LPA. 30 Overall, our data indicate that treatment of HIV-infected individuals with rhGH is associated with modest increases in naive CD4 þ T-lymphocytes, yet the origin of these naive cells and their impact on immune function require further investigation.…”

Differential Effects of Interleukin-7 and Interleukin-15 on NK Cell Anti-Human Immunodeficiency Virus Activity

“…IL-2 coadministered with ART causes nearly universal increases in CD4 T-cell and natural killer (NK) cell numbers (38). Yet despite increased T-cell numbers, vaccination responses were unchanged in a cohort of patients treated with ART and IL-2 compared to results with ART alone (71), suggesting that acquired immunity is not enhanced by IL-2 cotherapy. Furthermore, despite initial optimism that IL-2 would activate HIV from its latent reservoir and thereby enhance the ability of ART to cause a decline in the size of the HIV latent pool (15), this effect has not translated to viral eradication, even after 2 years of intense ART plus IL-2 therapy (59,66,78).…”

Impaired Monocyte Maturation in Response to CpG Oligodeoxynucleotide Is Related to Viral RNA Levels in Human Immunodeficiency Virus Disease and Is at Least Partially Mediated by Deficiencies in Alpha/Beta Interferon Responsiveness and Production

“…HIV disease presents a unique challenge for vaccine design since patients may experience profound CD4 cell loss with generalized immunodeficiency and impaired responsiveness to immunization (7,27,28). The potential for CpG ODNs to enhance CD8 T-cell responses independently of CD4 cell help (4,5) may therefore be particularly relevant to HIV disease.…”