Journal of Clinical and Cellular Immunology
Open Access

Abstract

CD4 T-cell Activation and Reduced Regulatory T-cell Populations are Associated with Early Development of Cataracts among HIV-infected Adults in Uganda

Damalie Nakanjako, Juliet Otiti-Sengeri, Isaac Ssewanyana, Rose Nabatanzi, Lois Bayigga, Samuel Kirimunda, Moses Joloba, Yukari C Manabe, Andrew Kambugu, Robert Colebunders and Harriet Mayanja-Kizza

Background: Cataracts contribute 12% of visual loss among HIV-infected adults (HIV-positive) in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-negative and HIV-positive individuals; thus the need for innovative therapeutic interventions for cataracts among HIV-positive adults. We compared the regulatory T-cell (Treg) dysfunction among HIV-positive-with-cataracts, HIV-negative-with-cataracts and respectively age-matched HIV-healthy-volunteers.

Methods: In a laboratory based case-control study, nested within a clinical/surgical community outreach camp, within the Rakai Health Sciences Program (RHSP) rural cohort, 50 adults with cataracts eligible for surgery were selected consecutively. Routine provider-initiated HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive adults with cataracts (cases) and HIV-negative adults with cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adultswithout- cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+bright and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups.

Results: Of 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44-53) years] than HIV-negative [70 (IQR 59-75) years]; p=0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p=0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p=0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive individuals with cataracts expressed higher levels of immune activation than HIV-positive individuals without cataracts; p=0.012 and HIV-negative individuals with cataracts expressed higher levels of immune activation that HIV-negative-withoutcataracts; p<0.0001.

Conclusion: CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.