AEGiS-11IAC: The role of CD8+ anti-CD4+ cytotoxic T Lymphocyte activity in controlling HIV infection.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

The role of CD8+ anti-CD4+ cytotoxic T Lymphocyte activity in controlling HIV infection.

Int Conf AIDS 1996 Jul 7-12; 11:210 (abstract no. Th.A.104)
Smaill FM, Gomez AM, McKay P, Leith J, Kelleher L, Rosenthal K; McMaster University Medical Centre, Hamilton, Ont., Canada. Fax: 905-521-5099. E-mail: smaill@fhs.csu.mcmaster.ca.

OBJECTIVE: To monitor the natural history of CD8+ anti-CD4+ cytotoxic T lymphocyte activity (CTL) in a cohort of HIV-positive persons and correlate this activity with clinical progression of HIV disease.

METHODS: HIV-positive subjects with CD4+ counts greater than or equal to 100/mm3 were studied. At enrollment and three monthly intervals, blood was collected for determination of CTL activity against autologous activated CD4+ lymphocytes. Lymphocytes were separated using OKT4 coated magnetic beads. Positively selected CD4+ lymphocytes were stimulated with PHA and used as targets; negatively selected CD8+ lymphocytes (greater than 90% pure) were used as effectors. Cytotoxicity was measured and quantified using a chromium release assay. At 3 monthly intervals, CD4+ and CD8+ lymphocyte counts were measured and the status of clinical disease was recorded. The primary analysis was the correlation of changes in CD4+ count over a 3 month time interval with the initial presence or absence of detectable anti-CD4+ activity; the secondary analysis was the correlation of the anti-CD4+ activity with clinical progression of disease.

RESULTS: 87 patients were studied from Sept 93 - May 95. Each patient on average contributed 3 intervals (range 1-7). In any one individual, CD8+ anti-CD4+ CTL fluctuated over time and could not be shown to be associated with changes in CD4+ count or disease progression. Overall, however, the absence of CD8+ anti-CD4+ CTL was associated with a greater drop in CD4+ count compared with the change in CD4+ count when the activity was present, a difference that was statistically significant (p is less than 0.05). There were too few clinical endpoints for any differences in clinical progression to be observed. No association between the level of cytotoxicity and the change in CD4+ count was seen.

CONCLUSION: In contrast to our previous cross-sectional study, this prospective study has demonstrated that the detection of CD8+ anti-CD4+ activity does not appear to be associated with a decline in CD4+ count. The presence of this activity may indeed indicate a functional immune system. Further correlation of this activity, including its effect on viral replication, is required.

Keywords: AEGIS, Antigens, CD8, Antigens, CD4, T-Lymphocytes, Cytotoxic, HIV Infections, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, HIV Seropositivity, Disease Progression, Lymphocyte Count, Virus Replication, Cross-Sectional Studies, Prospective Studies, Human, virology, ICA11

960707
ThA104