Evaluation of cellular immune responses in subjects chronically infected with HIV type 1.
The importance of host cellular immune responses, particularly CD8(+) cytotoxic T-lymphocyte (CTL) responses, in control of human immunodeficiency virus type 1 (HIV-1) infection has been demonstrated in many clinical studies. These studies, along with vaccination challenge studies in rhesus macaques, indicate the importance of cellular immune responses against HIV-1. Toward this end, we evaluated anti-HIV-1 cellular immune responses in a cohort of 54 subjects who were chronically infected with HIV-1. By validation of IFN-gamma ELISpot assay, we established a dual cut-off criterion for scoring a positive response. The magnitude and frequency of cellular immune responses were measured against HIV-1 antigens (Gag, Pol, Nef, Rev, and Tat), using synthetic peptides as antigens in ELISpot assay. Here we showed that HIV-1 Gag, Pol, and Nef were frequent targets of T cell responses in these subjects, whereas Tat and Rev were less frequently recognized. We further evaluated the possible association between host cellular immune responses and corresponding plasma viral loads in this cohort. By performing ranking correlation analysis, we demonstrated a positive correlation between host viral loads and ELISpot responses of HIV Gag and Pol in untreated subjects. For the subjects under antiviral regimens, however, we did not find any significant association. Our findings suggest that the high levels of ELISpot responses in chronically infected subjects were reflective of their persistent viral infection.
Fu
Tong-Ming
TM
Merck Research Laboratories, West Point, PA 19486, USA. tong-ming_fu@merck.com
Dubey
Sheri A
SA
Mehrotra
Devan V
DV
Freed
Daniel C
DC
Trigona
Wendy L
WL
Adams-Muhler
Lisa
L
Clair
James H
JH
Evans
Thomas G
TG
Steigbigel
Roy
R
Jacobson
Jeffrey M
JM
Goepfert
Paul A
PA
Mulligan
Mark J
MJ
Kalams
Spyros A
SA
Rinaldo
Charles
C
Zhu
Lan
L
Cox
Kara S
KS
Guan
Liming
L
Long
Romnie
R
Persaud
Natasha
N
Caulfield
Michael J
MJ
Sadoff
Jerald C
JC
Emini
Emilio A
EA
Thaler
Scott
S
Shiver
John W
JW
D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D012367:RNA, Viral / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D044465:White People / Q000706:statistics & numerical data; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015696:Gene Products, tat; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma