High levels of CD8-positive lymphocytes expressing CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV-infected individuals are not associated with increased mortality

Lymph nodes constitute the major site of HIV replication and of immunological response to HIV. To study the role of cytotoxic and mitotic active CD8⁺ lymphocytes in lymph nodes during HIV infection we examined 28 formalin-fixed, paraffin-embedded lymph nodes sampled from 1984 to 1986 from 21 HIV-seropositive patients and seven HIV-negative patients. Eleven of the HIV-positive patients died within 78 months of biopsy time and 10 patients were alive on July 1, 1998. Double immunohistochemical staining procedures were developed to identify CD8⁺ cells expressing CD45R0, granzyme B, and Ki-67. A stereological method was used to count the different cell types in the lymph nodes. There were no significant differences in the total cell (nucleated) and CD3⁺ cell concentrations between the three groups. However, there were significantly higher concentrations of CD3⁺CD8⁺, CD8⁺CD45R0⁺, and CD8⁺Ki-67⁺ lymphocytes in the HIV patients compared with the control group. Furthermore, there was a tendency for the HIV-deceased group to have lower levels of CD8⁺granzyme B⁺ and CD8⁺Ki-67⁺ lymphocyte concentrations compared with the HIV-alive group. Three HIV patients, who progressed to death within 49 months of biopsy time, were among the patients with the lowest concentrations of CD8⁺granzyme B⁺ and CD8⁺Ki-67⁺ lymphocytes. This finding allowed us to conclude that CD8⁺ lymphocytes expressing high levels of CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV patients are not related to increased mortality, whereas low concentrations of CD8⁺granzyme B⁺ and CD8⁺Ki-67⁺ lymphocytes may be associated with poor prognosis.