Functional Patterns of HIV-1-Specific CD4 T-Cell Responses in Children Are Influenced by the Extent of Virus Suppression and Exposure

Abstract

Correa R, Harari A, Vallelian F, et al. AIDS. 2007;21(1):23–30 PURPOSE OF THE STUDY. HIV-specific CD4+ T cells seem to play a critical role in antiretroviral immunity and particularly in maintaining cytotoxic T-cell responses. The objective of this study was to evaluate the function of HIV-specific T cells in antiviral treated, HIV-infected children. STUDY POPULATION. The researchers evaluated 23 HIV-infected children who were treated with antiretroviral therapy for a mean of 7 years. METHODS. Flow-cytometric analysis was used to measure the ability of HIV-specific T cells to secrete interleukin 2 (IL-2) and interferon γ (IFN-γ) after stimulation of patient cells with p55 gag protein. RESULTS. Three patterns of intracellular cytokine generation were identified: in 10 subjects, antigen-specific cytokine production was characterized by IL-2 production, 8 subjects’ CD4+ T cells expressed IL-2 and IFN-γ, and 5 subjects’ T cells expressed IFN-γ alone. These 3 groups were then analyzed for factors that might explain the different patterns. The patterns correlated with viral load at the time of functional analysis and over the previous 2 years. The group with dominant IFN-γ responses had high viremia levels, a pattern similar to that observed in patients with uncontrolled viral replication. Patients with combined IL-2 and IFN-γ production had relatively lower viral loads but had experienced viral “blips” over the 2 years before analysis. This pattern was similar to adults who were long-term nonprogressors or those whose conditions continued to progress despite antiretroviral therapy. The subjects with a dominant IL-2 response had very low levels of viremia and had not experienced viral “blips” over the previous 2 years. This pattern was similar to that generally observed in individuals who have cleared the infecting agent. It is important to note that this pattern has not been observed in HIV-infected adults. CONCLUSIONS. Children with HIV have a higher frequency of HIV-specific CD4+ T cells compared with adults, and their recovery of an IL-2–secreting T-cell pattern indicates a greater capacity for immune restoration in children than adults. REVIEWER COMMENTS. This elegant study provides a biological rationale for the clinical observation that young children started on antiretroviral therapy have the capacity for remarkable reconstitution of immune functions relative to those reported in adults and older children who have been infected for prolonged periods before antiretroviral therapy. Perhaps it is unfair to compare these results with findings in adults that included patients who were infected for many years before their initiation of therapy. A more appropriate comparative adult group would be those treated within 6 months of their diagnosis. Most importantly, this study demonstrates that children are “different” and that treatment early in infection allows excellent immune reconstitution if viral replication is completely controlled.