The role of race and gender in T cell responses in children perinatally infected with HIV-1.

Understanding the immunologic mechanisms that can control the progression of HIV disease is paramount for the development of vaccines or of new strategies for immunotherapy. Whether infection occurs perinatally, sexually, or parenterally, disease ultimately develops in all but a very few individuals, although the time to disease is quite variable. This tremendous variability in disease progression may be influenced by age at the time of infection, viral load, race, and host genetic factors, most notably HLA class and CCR5 [1–8]; however, the influence of gender is more controversial. Additionally, there is evidence that these same factors may also protect against infection in some individuals and in certain settings. Few studies have assessed the role of race, gender, and host genetic factors in children or adolescents, especially those infected perinatally. However, this population can offer unique clues for our understanding of the interrelationships between host genetic factors and changes in the immune and endocrine systems that occur from the time of transmission through puberty. This is especially important at present, because, worldwide, adolescent girls are becoming infected at an alarming rate and are having babies who are themselves infected. In this issue of the Journal of Infectious Diseases, Sharp et al. [9] have evaluated the influence of race and gender on HIV-1–spe-cific immune responses in a small case-control study of 41 perinatally infected African American and Hispanic children. Patients who were chosen for the study received their care at the same HIV center and were from the same community. They were matched for race, gender, HIV-1 RNA load, age, and CD4 + cell count. HIV-1–spe-cific T cell responses of cryopreserved cells were measured by use of an interleukin (IL)–7 and IL-15–amplified enzyme-linked immunospot (ELISPOT) assay with synthetic peptides of the clade B Gag, Nef, and Tat consensus sequences; HLA typing was also performed. Sharp et al. [9] made a number of intriguing observations. First, of the 18 matched pairs, total HIV-1–specific responses (the sum of the number of spot-forming cells for Gag, Nef, and Tat pep-tides) were higher in African American than in Hispanic children. This was driven primarily by the Gag response. Second , African American girls at or near puberty showed the highest HIV-1–spe-cific T cell responses. Finally, there was a trend toward higher Gag responses in children with A*66 and B*58 haplotypes. Trends were also noted for responses related to CD4 + cell count, viral load, and age, …