Development of antibodies to HIV-1 is associated with an increase in circulating CD3⁺ CD4^- CD8^- lymphocytes

This study investigated whether seroconversion with respect to human immunodeficiency virus, type 1 (HIV-1) was associated with an increase in lymphocytes expressing the CD3⁺ CD4^- CD8^- phenotype. Proportions and absolute numbers of CD3⁺, CD4⁺, and CD8⁺ lymphocytes were determined prospectively over a 2.5-year period on 4954 homosexual and/or bisexual men participating in the Multicenter AIDS Cohort Study. Of the 4808 men whose serostatus at entry could be verified, 1745 were seropositive (SP) for antibodies to HIV-1 at entry into study, 2795 were uniformly seronegative (SN) for HIV-1 for 30 months, and 268 were seroconverters (SC) with respect to HIV-1 during this period. For each of six semiannual evaluations, proportions and numbers of CD3⁺ CD4^- CD8^- lymphocytes (calculated as CD3 - (CD4 + CD8)) were both significantly greater in the SP group than in the SN group (P < 0.001). Mean CD3⁺ CD4^- CD8^- levels in the SC group were indistinguishable from those in the SN group before seroconversion, but by 3-9 months after seroconversion the SC group demonstrated absolute numbers of CD3⁺ CD4^- CD8^- lymphocytes which were significantly increased (P < 0.001) compared to the SN group using linear regression methods with adjustment for correlation of measurements within an individual over time. An additional significant increase occurred by 21-27 months after seroconversion (P = 0.006). These results are consistent with an association of HIV-1 seroconversion with an increase in circulating T lymphocytes expressing the CD3⁺ CD4^- CD8^- phenotype (double negative T cells), a decrease in CD3^- CD4^- CD8⁺ natural killer cells, or both. An increase in double negative T cells could reflect a host defense mechanism against HIV-1 or effects of HIV-1 on T cell development.