CD8+HLA/DR+ cells negative for CD38 antigen predict CD4+ counts and natural killer cell cytotoxicity while CD8+HLA/DR+ cells positive for CD38 antigen predict blastogenic responses to PHA in HIV-1 seropositive men and women
Date of Award
Doctor of Philosophy (Ph.D.)
First Committee Member
Barry E. Hurwitz, Committee Chair
Predominance of the highly cytotoxic CD8+HLA/DR+CD38+ cell has been associated with declines in T-helper cell counts while predominance of the CD8+HLA/DR+CD38-- phenotype, which is much less cytotoxic and a possible T-cell antiviral factor (CAF) secreting cell, has been associated with stable CD4+ cell counts and nonprogression during HIV-1 infection (Ho et al., 1993; Giorgi et al., 1994; Liu et al., 1997).The purpose of this study was to examine relationships between the CD38+ and CD38- phenotypes of the CD8+HLA/DR+ lineage with indicators of disease progression (CD4+ counts, HIV symptoms), other enumerative immune measures (CD8+, CD19+ counts), functional immune measures (blastogenic response to, PHA, NKCC), cardiovascular performance (cardiac output, total peripheral resistance), and cardiac autonomic integrity (myocardial contractility, respiratory sinus arrhythmia) at rest and during behavioral challenge. Predictive power using activated CD8+ subsets was compared with overall CD8+ cell counts.One hundred thirty-nine HIV-1 seropositive asymptomatic and symptomatic men and women of a variety of ethnic backgrounds participated in the present study. All samples were obtained during baseline, stress-period, and post-stressor phases of a reactivity protocol that assessed immune, cardiovascular, and neuroendocrine response to speech stressor. Multiple regression analyses were employed to examine the relationships discussed above. Interactions between recently diagnosed subjects and those who have been diagnosed for more than 12 months with CD8+HLA/DR+CD38+/- cell counts were also included in the models.Results indicated that CD8+HLA/DR+CD38- cells predicted CD4+ cell counts only in subjects diagnosed for more than 12 months (p < .003), even after controlling for overall CD8+ cell counts. CD8+HLA/DR+CD38- counts significantly predicted declines in NKCC, while CD8+HLA/DR+CD38+ predicted declines in responses to PHA, even after controlling for disease progression (CD4+ counts and HIV symptoms) and strew hormone levels (ACTH, cortisol, epinephrine, norepinephrine), regardless of diagnosis date. The use of predictor variables obtained from reactivity data were not predictive of CD4+ cell counts, NKCC, or blastogenic responses to PHA. No relationships between the activated CD8+ cell counts were found with cardiovascular or autonomic functioning after controlling for age, gender, and body mass index.This study gives support to the hypothesis that greater CD8+HLA/DR+CD38- counts are related to improved control over HIV-1 infection and have different functional roles from CD8+HLA/DR+CD38+ cells.
Psychology, Clinical; Health Sciences, Immunology; Psychology, Physiological
Milanovich, John Robert, "CD8+HLA/DR+ cells negative for CD38 antigen predict CD4+ counts and natural killer cell cytotoxicity while CD8+HLA/DR+ cells positive for CD38 antigen predict blastogenic responses to PHA in HIV-1 seropositive men and women" (1999). Dissertations from ProQuest. 3788.